Pathogenesis and Biomarker Research in Traumatic Brain Injury

Traumatic brain injury (TBI) refers to structural and functional damage to brain tissue caused by external force applied to the head. Its pathological process does not end with the mechanical destruction that occurs at the moment of injury, but progresses from primary injury to secondary injury. Secondary injury involves multiple processes, including energy metabolism disorder, excitotoxicity, calcium overload, mitochondrial dysfunction, oxidative stress, neuroinflammation, blood-brain barrier disruption, and axonal injury. These mechanisms are important drivers of the continued progression of neurological deficits after TBI.

Keywords: traumatic brain injury; TBI; diffuse axonal injury; neuroinflammation; blood-brain barrier; GFAP; UCH-L1; NfL; S100B

1 Basic Concepts of Traumatic Brain Injury

1.1 Definition of TBI

Traumatic brain injury refers to structural damage and functional impairment of brain tissue after the head is exposed to impact, acceleration-deceleration, rotation, blast, or penetrating external force. Its manifestations cover a wide range, from mild concussion, transient disturbance of consciousness, headache, and cognitive decline to severe cerebral contusion and laceration, intracranial hematoma, cerebral edema, coma, and long-term neurological dysfunction.

The pathological feature of TBI is dynamic evolution. Primary injury occurs at the moment of external force exposure and is mainly caused by mechanical tearing, contusion, shearing, and vascular rupture. Secondary injury continues to develop over minutes to days or even longer and is jointly driven by molecular, cellular, and inflammatory cascades.

1.2 Primary Injury and Secondary Injury

(1) Primary injury

Primary injury is direct brain tissue damage caused by external force, including cerebral contusion and laceration, intracranial hemorrhage, diffuse axonal injury, cerebrovascular injury, local tissue tearing, and traction of nerve fiber tracts. Its severity is related to the direction, intensity, duration of force, mode of head movement, and distribution of mechanical stress within brain tissue.

(2) Secondary injury

Secondary injury is a continuous pathological process that occurs on the basis of primary injury. After mechanical injury, neurons, glial cells, vascular endothelial cells, and immune cells are activated sequentially and release glutamate, ROS, inflammatory factors, and damage-associated molecular patterns, leading to excitotoxicity, oxidative stress, blood-brain barrier disruption, cerebral edema, and multiple forms of cell death.

(3) Neurological deficits

Neurological deficits after TBI may arise from multiple levels. Neuronal death reduces information-processing capacity, axonal injury disrupts neural network connectivity, oligodendrocyte and myelin injury reduces conduction efficiency, and blood-brain barrier disruption and inflammatory responses further expand the injury range.

Table 1 Differences Between Primary Injury and Secondary Injury in TBI

Type	Time of Occurrence	Main Mechanisms	Pathological Significance
Primary injury	Moment of external force exposure	Contusion, shearing, tearing, hemorrhage, axonal traction	Determines the initial injury range
Secondary injury	Minutes to days after injury	Excitotoxicity, inflammation, oxidative stress, cerebral edema, cell death	Determines injury progression and functional outcome
Repair and remodeling	Subacute to chronic phase	Glial response, limited axonal regeneration, synaptic remodeling, inflammation resolution	Influences long-term recovery and sequelae

2 Major Pathological Injury Types in TBI

2.1 Focal Brain Injury

(1) Cerebral contusion and laceration

Cerebral contusion and laceration often occur at the impact site or contrecoup site and frequently involve mechanically vulnerable regions such as the frontal and temporal lobes. Local tissues may show hemorrhage, necrosis, edema, and neuronal loss. The surrounding region of cerebral contusion and laceration often shows secondary inflammation and blood-brain barrier disruption, which are important sources of injury expansion and neurological dysfunction.

(2) Intracranial hemorrhage

TBI can cause epidural hematoma, subdural hematoma, subarachnoid hemorrhage, and intraparenchymal hemorrhage. Hemorrhage not only produces a mass effect, but also aggravates brain tissue injury through hemoglobin degradation products, iron loading, oxidative stress, and inflammatory responses.

(3) Cerebral edema

Cerebral edema includes cytotoxic edema and vasogenic edema. Cytotoxic edema is mainly caused by energy metabolism disorder and ion pump failure, whereas vasogenic edema is associated with blood-brain barrier disruption and plasma component leakage. Cerebral edema can increase intracranial pressure, compress brain tissue and cerebral blood vessels, and further reduce cerebral perfusion.

2.2 Diffuse Axonal Injury

(1) Axonal shear injury

Diffuse axonal injury is a common and critical form of injury in TBI. Because axonal fiber tracts are long and highly sensitive to stretching, rotational, and shearing forces, rapid acceleration-deceleration or rotation of the head can cause axonal stretching, microtubule disruption, and impaired axoplasmic transport.

(2) Axonal swelling and disconnection

After axoplasmic transport is blocked, proteins and organelles accumulate within axons, forming axonal swelling. If injury continues to progress, secondary axonal disconnection may occur. Impaired axonal connectivity disrupts information transmission between brain regions. Even when imaging does not show obvious focal hemorrhage, abnormalities in cognition, attention, memory, and emotional regulation may occur.

(3) NfL and axonal injury

Neurofilament light chain (NfL/NFL) is an important component of the axonal cytoskeleton. After axonal injury, NfL can be released into cerebrospinal fluid and blood. Therefore, it is considered an important biomarker reflecting acute and chronic neuroaxonal injury.

2.3 Neurovascular Unit Injury

(1) Blood-brain barrier disruption

After TBI, cerebral microvascular endothelial cells, tight junction proteins, basement membrane, pericytes, and astrocytic endfeet can all be damaged. Once blood-brain barrier permeability increases, plasma proteins, inflammatory cells, and water enter the brain parenchyma, resulting in vasogenic edema and inflammatory spread.

(2) Microcirculatory disturbance

Post-traumatic vasospasm, microthrombus formation, endothelial swelling, and local hypoperfusion can all cause microcirculatory disturbance. Microcirculatory disturbance aggravates local hypoxia, energy metabolism insufficiency, and secondary neuronal injury.

(3) Glial cell responses

Astrocytes and microglia are rapidly activated after TBI. Astrocytes participate in blood-brain barrier repair, glutamate clearance, and glial scar formation. Microglia participate in immune surveillance, phagocytosis of cellular debris, and inflammatory factor release. Glial responses are protective, but excessive activation may aggravate neuroinflammation.

3 Molecular Mechanisms of Secondary Injury in TBI

3.1 Excitotoxicity

(1) Abnormal glutamate release

After TBI, mechanical injury and energy metabolism disorder can cause neuronal depolarization and promote massive glutamate release. At the same time, astrocytic glutamate uptake decreases, resulting in sustained elevation of extracellular glutamate concentration.

(2) Overactivation of glutamate receptors

Excess glutamate can continuously activate NMDA receptors and AMPA receptors, causing Ca²⁺ and Na⁺ influx. Excessive receptor activation transforms normal excitatory neurotransmission into cytotoxic signaling, leading to intracellular calcium overload, mitochondrial injury, and abnormal activation of enzyme systems.

(3) Calcium overload

Excessive intracellular Ca²⁺ can activate calpains, phospholipases, endonucleases, and nitric oxide synthase, leading to cytoskeletal degradation, membrane lipid injury, DNA damage, and abnormal NO generation. Calcium overload is also an important link among axonal injury, mitochondrial injury, and cell death.

3.2 Mitochondrial Dysfunction and Energy Metabolism Disorder

(1) Decreased ATP production

Neurons are highly dependent on mitochondrial oxidative phosphorylation. After TBI, decreased mitochondrial membrane potential, respiratory chain damage, and calcium overload reduce ATP production. ATP deficiency impairs ion pump function, further causing membrane depolarization, cellular edema, and abnormal neurotransmitter release.

(2) Increased ROS generation

After mitochondrial damage, electron leakage occurs in the electron transport chain, producing ROS such as superoxide. ROS can oxidize lipids, proteins, and nucleic acids, disrupt cellular structures, and amplify neuroinflammatory and cell death signaling.

(3) Metabolic imbalance

After TBI, brain tissue may show glucose metabolism disorder, lactate accumulation, changes in the NAD⁺/NADH ratio, and local acidosis. Deterioration of the metabolic environment affects neuronal excitability, enzyme activity, and cellular repair capacity, allowing injury to expand from the local region to surrounding tissues.

3.3 Oxidative Stress and Lipid Peroxidation

(1) Sources of free radicals

Sources of ROS and RNS after TBI include damaged mitochondria, NADPH oxidase, respiratory burst of inflammatory cells, abnormal activation of nitric oxide synthase, and hemoglobin degradation products. Free radicals from multiple sources jointly drive persistent oxidative stress.

(2) Lipid peroxidation

Brain tissue is rich in polyunsaturated fatty acids and is easily attacked by ROS. Lipid peroxidation damages cell membranes, mitochondrial membranes, and myelin structures and produces reactive products such as MDA and 4-HNE, which further modify proteins and amplify injury.

(3) Decline in antioxidant defense

Antioxidant systems such as GSH, SOD, CAT, GPx, Trx, and Prx can buffer oxidative stress. After TBI, if ROS production exceeds clearance capacity, antioxidant defenses become imbalanced, and neurons and glial cells are more likely to enter apoptosis, necrosis, or ferroptosis.

3.4 Neuroinflammation

(1) Microglial activation

After TBI, microglia can recognize cellular debris, ATP leakage, HMGB1, and other damage-associated signals and rapidly become activated. Activated microglia release TNF-α, IL-1β, IL-6, NO, and ROS. They participate in clearing injured tissue but may also aggravate neuronal injury.

(2) Peripheral immune cell infiltration

After blood-brain barrier disruption, neutrophils, monocytes, and lymphocytes can enter brain tissue. Peripheral immune cells release proteases, cytokines, and free radicals, further aggravating local inflammation and vascular injury.

(3) Bidirectional effects of inflammation

Neuroinflammation is not entirely harmful. Moderate inflammation helps clear necrotic tissue and initiate repair, whereas sustained or excessive inflammation causes secondary injury. TBI research should focus on the timing of inflammation, cell types, spatial distribution, and phenotypic transitions.

3.5 Blood-Brain Barrier Disruption and Cerebral Edema

(1) Tight junction disruption

Inflammatory factors, MMP activation, ROS, and mechanical stretch can disrupt tight junction-associated structures such as ZO-1, occludin, and claudin-5, increasing blood-brain barrier permeability.

(2) Vasogenic edema

After blood-brain barrier disruption, plasma proteins and water leak into the brain parenchyma, forming vasogenic edema. Edema increases local pressure, compresses microvessels, reduces cerebral perfusion, and further amplifies ischemic-hypoxic injury.

(3) Increased intracranial pressure

In severe TBI, cerebral edema, hemorrhage, and abnormal blood flow regulation can jointly lead to increased intracranial pressure. Increased intracranial pressure reduces cerebral perfusion pressure and increases the risk of secondary ischemia.

3.6 Cell Death Modes

(1) Necrosis

Severe mechanical injury and acute energy depletion can cause cell membrane rupture and necrosis. Necrotic cells release DAMPs, further activating microglia and peripheral immune cells.

(2) Apoptosis

Mitochondrial injury, DNA damage, and death receptor signaling can activate the caspase cascade, leading to apoptosis of neurons and glial cells. Apoptosis is commonly observed in peri-lesional regions and during the secondary injury phase.

(3) Pyroptosis

Inflammasome activation can promote Caspase-1, IL-1β, IL-18, and GSDMD-related signaling and induce inflammatory cell death. Pyroptosis connects cell death with inflammation amplification.

(4) Ferroptosis

Ferroptosis is associated with iron homeostasis disturbance, GSH depletion, reduced GPx4 function, and lipid peroxidation. After TBI, hemorrhage, iron release, and oxidative stress may all increase the risk of ferroptosis.

Table 2 Mechanisms and Key Readouts of Secondary Injury in TBI

Mechanistic Link	Main Changes	Common Research Readouts
Excitotoxicity	Increased glutamate, overactivation of NMDA/AMPA receptors	Glutamate, NMDA receptors, Ca²⁺ signaling
Calcium overload	Increased Ca²⁺ influx and activation of calcium-dependent enzymes	Calcium imaging, calpain, nNOS
Mitochondrial dysfunction	Decreased membrane potential, reduced ATP, increased ROS	JC-1, ATP, MitoSOX, oxygen consumption rate
Oxidative stress	Increased ROS/RNS and lipid peroxidation	ROS, MDA, 4-HNE, 8-OHdG, GSH/GSSG
Neuroinflammation	Activation of microglia and peripheral immune cells	Iba1, TNF-α, IL-1β, IL-6, NLRP3
Blood-brain barrier disruption	Tight junction disruption and vascular leakage	Evans blue, ZO-1, occludin, claudin-5
Axonal injury	Impaired axoplasmic transport and neurofilament release	APP accumulation, NfL, Tau
Cell death	Necrosis, apoptosis, pyroptosis, ferroptosis	LDH, Caspase-3, GSDMD, GPx4, ACSL4

4 Importance of Biomarker Research in TBI

4.1 Why TBI Biomarkers Are Needed

(1) Complex pathological mechanisms

TBI injury simultaneously involves neurons, axons, astrocytes, oligodendrocytes, vascular endothelium, and immune cells. A single imaging examination or single symptom cannot fully reflect injury type and progression. Therefore, biomarker panels that reflect different cellular sources and pathological processes are needed.

(2) Difficulty in identifying mild TBI

Patients with mild TBI or concussion may have no obvious structural imaging abnormalities, but axonal injury, metabolic abnormalities, and neuroinflammation may still be present. Blood or cerebrospinal fluid biomarkers help capture neural injury signals at the molecular level.

(3) Need for prognostic evaluation

After TBI, the duration of symptoms, cognitive recovery, motor function recovery, and long-term neurodegenerative risk vary widely. Dynamic biomarker detection can help study injury burden, recovery trajectory, and subsequent risk.

4.2 Sample Sources for Biomarkers

(1) Cerebrospinal fluid

Cerebrospinal fluid is closer to the central nervous system environment, and biomarker concentration changes are more sensitive. It is suitable for mechanistic studies and severe TBI research. However, cerebrospinal fluid collection is invasive and is not suitable for all research scenarios.

(2) Blood

Blood samples include serum and plasma. They are easy to collect and suitable for acute-phase dynamic monitoring and large-sample studies. Because blood biomarker results are affected by the blood-brain barrier, peripheral tissue sources, and protein clearance kinetics, they should be interpreted together with the time window and clinical background.

(3) Multi-marker combination

TBI is not injury to a single cell type. Combined detection of GFAP, UCH-L1, S100B, NfL, Tau, and other biomarkers can evaluate TBI from different perspectives, including astrocyte injury, neuronal soma injury, axonal injury, and blood-brain barrier disruption.

5 Biomarkers Related to TBI and Acute Neuronal Injury

5.1 GFAP

GFAP is an intermediate filament protein in astrocytes and mainly reflects astrocyte injury and glial responses. After TBI, damaged or activated astrocytes can release GFAP into cerebrospinal fluid and blood. GFAP has research value in identifying brain parenchymal injury, evaluating injury severity, and assisting assessment of imaging-positive risk.

5.2 UCH-L1

UCH-L1 is mainly expressed in neuronal cell bodies and axons and is a protein associated with the ubiquitin-proteasome system. After neuronal injury, UCH-L1 can be released into body fluids and is commonly used to reflect acute neuronal soma injury. Combined detection of GFAP and UCH-L1 can assess TBI injury from both glial and neuronal perspectives.

5.3 S100B

S100B is mainly derived from astrocytes but may also be affected by blood-brain barrier disruption and peripheral tissue sources. Increased S100B after TBI may indicate glial injury or increased blood-brain barrier permeability, but its specificity is affected by skeletal muscle, adipose tissue, and peripheral injury. Therefore, it is more suitable for interpretation in combination with other brain-specific biomarkers.

5.4 NfL/NFL

NfL is an important structural protein of axonal neurofilaments and can enter cerebrospinal fluid and blood after axonal injury. Because diffuse axonal injury is very common in TBI, NfL is considered an important marker of acute and subacute axonal injury. Changes in its level may also be related to research on persistent symptoms, recovery after sports-related concussion, and long-term neurodegenerative risk.

5.5 Tau Protein

Tau protein is associated with axonal microtubule stability. After TBI, axonal injury and microtubule disruption can lead to Tau release. Tau-related changes are also commonly investigated in studies of repetitive mild TBI and chronic traumatic encephalopathy. Tau biomarkers should be interpreted together with assay method, sample collection time point, and phosphorylation status.

5.6 NSE and MBP

NSE mainly reflects neuronal injury, but hemolysis and other factors may affect its detection results. MBP is a myelin-associated protein and can be used in studies of oligodendrocyte and myelin injury. Both can serve as supplementary indicators to improve evaluation of neuronal and white matter injury.

Table 3 TBI-Related Biomarkers and Research Significance

Biomarker	Main Source	Reflected Injury Type	Research Significance
GFAP	Astrocytes	Glial cell injury and brain parenchymal injury	Evaluates astrocytic response and structural brain injury
UCH-L1	Neuronal soma and axons	Acute neuronal injury	Reflects neuronal soma injury and is suitable for acute-phase studies
S100B	Astrocytes and some peripheral tissues	Glial injury and blood-brain barrier disruption	Sensitive but affected by peripheral injury in specificity
NfL/NFL	Axonal neurofilaments	Axonal injury and diffuse axonal injury	Suitable for evaluating acute and persistent axonal injury
Tau	Axonal microtubule-associated protein	Axonal cytoskeletal injury	Used in axonal injury and repetitive TBI research
NSE	Neurons	Neuronal injury	Can serve as a supplementary indicator of neuronal injury
MBP	Oligodendrocytes/myelin	Myelin and white matter injury	Used in white matter injury and demyelination studies

6 Time Windows and Interpretation of TBI Biomarkers

6.1 Acute Phase

Within hours after TBI, biomarkers such as UCH-L1 and GFAP may increase early, indicating neuronal and astrocytic injury. Acute-phase detection is more suitable for evaluating the presence of injury and initial severity, but results are easily affected by sampling time, blood-brain barrier status, and peripheral injury.

6.2 Subacute Phase

In the subacute phase, axon-related biomarkers such as NfL and Tau may better reflect persistent axonal injury and axoplasmic transport disturbance. Changes in biomarkers at this stage have research value for evaluating persistent symptoms, cognitive dysfunction, and white matter injury.

6.3 Chronic Phase

Chronic-phase TBI research focuses more on neurodegenerative changes, persistent inflammation, abnormal synaptic remodeling, and accumulation of repetitive injury. NfL, Tau, inflammatory factors, and imaging-based white matter indicators can be used together to evaluate long-term neural injury and recovery status.

6.4 Principles for Combined Interpretation

TBI biomarkers cannot be interpreted independently from injury type, time window, and sample type. GFAP is more oriented toward glial cells and structural brain injury, UCH-L1 toward acute neuronal injury, NfL toward axonal injury, and S100B is more strongly affected by peripheral sources. Multi-marker combinations are more suitable than a single biomarker for reflecting the multifactorial pathological mechanisms of TBI.

Table 4 Time-Window Characteristics of TBI Biomarkers

Time Phase	Main Biomarkers of Interest	Key Interpretation Focus
Acute phase	GFAP, UCH-L1, S100B	Determines early neuronal/glial cell injury
Subacute phase	NfL, Tau, MBP	Evaluates axonal injury, white matter injury, and persistent lesions
Chronic phase	NfL, Tau, inflammation-related indicators	Observes long-term neural injury and recovery status
Multi-marker combination	GFAP, UCH-L1, NfL, S100B, Tau	Evaluates neuronal, glial, axonal, and barrier injury from multiple perspectives

7 Experimental Models and Evaluation Indicators in TBI Mechanistic Research

7.1 Common Experimental Models

(1) Controlled cortical impact model

The controlled cortical impact model produces focal brain injury by setting impact velocity, depth, and duration. It is suitable for studying cerebral contusion, local hemorrhage, cortical neuronal death, inflammation, and functional recovery.

(2) Fluid percussion injury model

The fluid percussion injury model uses an instantaneous pressure wave applied to brain tissue and can simulate mixed focal and diffuse injury. It is suitable for studying cerebral edema, axonal injury, inflammatory responses, and cognitive impairment.

(3) Weight-drop model

The weight-drop model is relatively simple to perform and can simulate closed-head injury and concussion-like injury. Model outcomes are strongly affected by drop height, weight, contact area, and fixation method, so strict standardization is required.

(4) Blast injury model

The blast model is used to simulate TBI caused by shock waves and is commonly applied in military medicine and blast-related brain injury research. This model places greater emphasis on pressure waves, vascular injury, axonal injury, and neuroinflammation.

7.2 Histological Evaluation

Histological evaluation of TBI may include HE staining, Nissl staining, TUNEL, immunohistochemistry, and immunofluorescence. NeuN is used to observe neuronal survival, GFAP for astrocytic responses, Iba1 for microglial activation, MBP for myelin injury, and APP or NfL for axonal injury evaluation.

7.3 Molecular and Functional Evaluation

Molecular indicators may include ROS, MDA, 4-HNE, GSH/GSSG, ATP, mitochondrial membrane potential, inflammatory factors, apoptotic proteins, ferroptosis-related proteins, and blood-brain barrier-related proteins. Behavioral evaluation can combine motor coordination, learning and memory, anxiety-like behavior, sensory function, and cognitive function tests.

Table 5 Common Evaluation Modules in TBI Research

Research Module	Common Indicators	Main Significance
Tissue injury	HE, Nissl, TUNEL, cerebral edema content	Determines structural injury and cell death
Neuronal injury	NeuN, UCH-L1, NSE	Evaluates neuronal loss and acute injury
Axonal injury	NfL, Tau, APP, MBP	Evaluates axonal injury and white matter damage
Glial response	GFAP, Iba1, S100B	Evaluates activation of astrocytes and microglia
Oxidative stress	ROS, MDA, 4-HNE, 8-OHdG, GSH/GSSG	Determines oxidative injury and antioxidant capacity
Inflammatory response	TNF-α, IL-1β, IL-6, NLRP3	Evaluates the degree of neuroinflammation
Blood-brain barrier	Evans blue, ZO-1, occludin, claudin-5	Determines barrier disruption and vascular leakage
Mitochondrial function	ATP, JC-1, oxygen consumption rate, MitoSOX	Evaluates energy metabolism and mitochondrial ROS
Behavioral function	Rotarod, water maze, open field, novel object recognition	Evaluates motor, cognitive, and emotion-related functions

Table 6 Products for Biomarker Detection, Glial Response, Axonal Injury, and Blood-Brain Barrier Evaluation in Traumatic Brain Injury Research

Research Module	Catalog No.	Product Name	Grade & Purity	Application Positioning
Astrocyte injury/GFAP	Ab105229	GFAP Antibody	Carrier Free, ExactAb™, Azide Free, Validated, High Performance, See COA	Detection of GFAP expression to evaluate astrocyte injury and gliosis after TBI
Astrocyte injury/GFAP	Ab179925	GFAP Mouse mAb	Carrier Free, ExactAb™, Azide Free, Validated, High Performance, PBS Only, See COA	GFAP detection by IHC, IF, or WB for glial response analysis
Astrocyte injury/GFAP	Ab156546	GFAP Mouse mAb	Carrier Free, ExactAb™, Azide Free, Validated, High Performance, PBS Only, 1.0 mg/mL	Detection of astrocyte activation in TBI tissue
Astrocyte injury/GFAP	Ab179926	GFAP Mouse mAb	Carrier Free, ExactAb™, Azide Free, Validated, High Performance, PBS Only, 0.5 mg/mL	GFAP-related histological or protein expression analysis
Astrocyte injury/GFAP	Ab179924	GFAP Mouse mAb	Carrier Free, ExactAb™, Azide Free, Validated, High Performance, PBS Only, 0.5 mg/mL	Analysis of glial injury and glial scar-related changes
GFAP mechanism validation	G1488399	GFAP Human Pre-designed siRNA Set A		GFAP knockdown for validating astrocyte response-related mechanisms
GFAP assay control	P746275	pLenti-GFAP-sgRNA		Negative control material for GFAP antibody specificity or WB validation
GFAP assay control	P746276	pLenti-GFAP-sgRNA		Negative control for GFAP transcript-level assay validation
GFAP standard/antigen	rp156642	Recombinant Human GFAP Protein	Carrier Free, Azide Free, His Tag, ≥95%(SDS-PAGE)	Recombinant antigen or positive control for GFAP detection systems
GFAP standard/antigen	rp329436	Recombinant Human Glial Fibrillary Acidic/GFAP Protein	≥90%(SDS-PAGE)	GFAP-related antibody validation, immunoassay development, or assay control
GFAP fluid biomarker	EJ1514471	Human Glial Fibrillary Acidic Protein (GFAP) ELISA Kit	BioReagent	Measurement of GFAP in human serum, plasma, or CSF
GFAP fluid biomarker	EJ1512977	Mouse Glial Fibrillary Acidic Protein (GFAP) ELISA Kit	BioReagent	Measurement of GFAP in mouse TBI models
Neuronal injury/UCH-L1	L137664	LDN-57444	≥98%(HPLC)	Mechanistic intervention for UCH-L1-related neuronal injury studies
Neuronal injury/UCH-L1	rp183597	Recombinant Human UCH-L1/PGP9.5 Protein	Carrier Free, His Tag, ≥95%(SDS-PAGE)	Recombinant protein control for UCH-L1 assay systems
Neuronal injury/UCH-L1	EJ1514234	Human Ubiquitin Carboxyl Terminal Hydrolase L1 (Uch-L1) ELISA Kit	BioReagent	Detection of UCH-L1 as an acute neuronal injury biomarker
Glial injury/S100B	rp156671	Recombinant Human S100B Protein	Carrier Free, Bioactive, ActiBioPure™, Azide Free, His Tag, PBS Only, ≥95%(SDS-PAGE)	Recombinant protein or standard for S100B detection systems
Glial injury/S100B	rp329857	Recombinant Rat S100B Protein	≥90%(SDS-PAGE)	Assay development or detection control for rat S100B
Glial injury/S100B	S1478321	S100B Human Pre-designed siRNA Set A		S100B knockdown for validating glial injury or barrier-related mechanisms
Glial injury/S100B	Ab008407	S100B Mouse mAb	Carrier Free, ExactAb™, Azide Free, Validated, PBS Only, See COA	Immunodetection of S100B to evaluate glial injury
Glial injury/S100B	Ab008408	S100B Mouse mAb	Carrier Free, ExactAb™, Azide Free, Validated, PBS Only, See COA	Tissue or protein expression analysis of S100B
Glial injury/S100B	EJ1513621	Human S100 Calcium Binding Protein B (S100B) ELISA Kit	BioReagent	Measurement of S100B in human samples to assess glial injury and BBB disruption
Glial injury/S100B	EJ1511752	Rabbit S100 Calcium Binding Protein B (S100B) ELISA Kit	BioReagent	Measurement of S100B in rabbit samples
Glial injury/S100B	EJ1511909	Rat S100 Calcium Binding Protein B (S100B) ELISA Kit	BioReagent	Measurement of S100B in rat TBI models
Glial injury/S100B	EJ1512552	Mouse S100 Calcium Binding Protein B (S100B) ELISA Kit	BioReagent	Measurement of S100B in mouse TBI models
Axonal injury/Tau	EJ1513652	Human Tau Protein (Tau) ELISA Kit	BioReagent	Detection of total Tau in human samples to assess axonal cytoskeletal injury
Axonal injury/Tau	H1510027	Human Tau ELISA Kit	BioReagent	Quantitative detection of human Tau protein
Axonal injury/p-Tau	EJ1514439	Human Phosphorylated Tau-217 Protein(p-Tau217) ELISA Kit	BioReagent	Detection of p-Tau217 for repeated TBI and neurodegeneration-related research
Axonal injury/p-Tau	EJ1514440	Human Phosphorylated Tau181 Protein (p-TAU181) ELISA Kit	BioReagent	Detection of p-Tau181 to evaluate abnormal Tau phosphorylation
Axonal injury/p-Tau	EJ1514442	Human Phosphorylation Tau Protein (p-Tau) ELISA Kit	BioReagent	Detection of p-Tau in human samples
Axonal injury/p-Tau	EJ1514441	Human Phosphorylated Tau231 Protein (231P-tau) ELISA Kit	BioReagent	Detection of p-Tau231 to support Tau-related axonal injury analysis
Axonal injury/Tau	EJ1511913	Rat Tau Protein (Tau) ELISA Kit	BioReagent	Detection of Tau in rat TBI models
Axonal injury/Tau	EJ1512559	Mouse Microtubule Associated Protein Tau/Tau Protein(Tau) ELISA Kit	BioReagent	Detection of Tau in mouse TBI models
Axonal injury/p-Tau	EJ1512964	Mouse Phosphorylated Tau217 Protein (p-Tau217) ELISA Kit	BioReagent	Detection of p-Tau217 in mouse models
Axonal injury/p-Tau	EJ1512965	Mouse Phosphorylated Tau181 Protein (p-TAU181) ELISA Kit	BioReagent	Detection of p-Tau181 in mouse models
Axonal injury/p-Tau	EJ1512966	Mouse Phosphorylation Tau Protein (p-Tau) ELISA Kit	BioReagent	Detection of p-Tau in mouse samples
Axonal injury/Tau	EJ1511806	Monkey Total TAU Protein(T-TAU) ELISA Kit	BioReagent	Detection of total Tau in non-human primate TBI studies
Axonal injury/p-Tau	EJ1511813	Monkey Phosphorylated Tau-217 Protein(p-Tau217) ELISA Kit	BioReagent	Detection of p-Tau217 in non-human primate samples
Axonal injury/p-Tau	EJ1511814	Monkey Phosphorylated Tau181 Protein (p-TAU181) ELISA Kit	BioReagent	Detection of p-Tau181 in non-human primate samples
Axonal injury/APP	rp217612	Recombinant Human APP-1 Protein	Carrier Free, ≥95%(SDS-PAGE), expressed in E. coli; See COA	Recombinant protein control for APP-related assay systems
Axonal injury/APP	rp217154	Recombinant Human APP/Protease Nexin II Protein	Animal Free, Carrier Free, His Tag, PBS Only, ≥95%(SDS-PAGE), See COA	Assay development or control material for APP/axonal transport impairment studies
Axonal injury/APP	rp231120	Recombinant Human APP/Protease Nexin II Protein	Carrier Free, His Tag, SUMO tag, ≥85%(SDS-PAGE), expressed in E. coli; See COA	APP-related mechanistic research or detection control
White matter/myelin injury	Ab116654	Myelin Basic Protein/MBP Antibody	See COA	Detection of MBP to evaluate myelin injury and white matter damage after TBI
White matter/myelin injury	rp329552	Recombinant Human MBP Protein	≥90%(SDS-PAGE)	Recombinant protein control for MBP detection systems
Neuronal injury/NeuN	Ab117624	NeuN Antibody	Recombinant, ExactAb™, Validated, See COA	Detection of neuronal survival and neuronal loss
Neuronal injury/NeuN	rp170118	Recombinant Human NeuN Protein	Carrier Free, Azide Free, His Tag, ≥95%(SDS-PAGE)	Recombinant protein control for NeuN-related detection
Axonal/neurite injury supplemental marker	Ab327277	Recombinant Collapsin response mediator protein 1 Antibody	KD Validation	Supplemental marker for neurite injury, axon guidance, and neural repair studies
Neuronal injury/NSE	Ab118791	Recombinant NSE Antibody	Recombinant, ExactAb™, Validated, High Performance, See COA	Detection of NSE to support neuronal injury evaluation
Microglial activation/Iba1	Ab156545	Iba1 Mouse mAb	Animal Free, Carrier Free, ExactAb™, Azide Free, Validated, High Performance, PBS Only, ≥95%(SDS-PAGE), 1.0 mg/mL	Detection of microglial activation and neuroinflammation
Microglial activation/Iba1	rp156641	Recombinant Human AIF-1/Iba1 Protein	Carrier Free, Azide Free, His Tag, PBS Only, ≥90%(SDS-PAGE)	Recombinant protein control for Iba1 detection systems
Microglial activation/Iba1	Ab109181	Recombinant Iba1 Antibody	Recombinant, ExactAb™, Validated, See COA	Immunodetection of microglia
Microglia/macrophage response	Ab095179	CD68 Antibody	Carrier Free, ExactAb™, Validated, 1.0 mg/mL	Detection of CD68 to assess phagocytic microglia/macrophage activation
Microglia/macrophage response	C1478440	CD68 Human Pre-designed siRNA Set A		CD68 knockdown for validating phagocytic or inflammatory mechanisms
Microglia/macrophage response	Ab095183	Recombinant CD68 Antibody	Recombinant, ExactAb™, Validated, 0.24 mg/mL	CD68-related immunodetection
Microglia/macrophage response	rp329306	Recombinant Human CD68 Protein	≥90%(SDS-PAGE)	Recombinant protein control for CD68 detection systems
Microglia/macrophage response	rp175904	Recombinant Human CD68 Protein	Animal Free, Carrier Free, Azide Free, His Tag, PBS Only, ≥90%(SDS-PAGE)	Method development or positive control for CD68-related assays
Microglia/macrophage response	H1510045	Human CD68/SR-D1 ELISA Kit	BioReagent	Detection of CD68 in human samples to evaluate inflammatory cell activation
Microglia/macrophage response	EJ1512480	Mouse Cluster Of Differentiation 68 (CD68) ELISA Kit	BioReagent	Detection of CD68 in mouse TBI models
Mechanosensitive pathway	EJ1514183	Human Mechanosensitive Ion Channel PIEZO-1 (PIEZO-1) ELISA Kit	BioReagent	Detection of PIEZO-1 for mechanical force sensing and mechanical brain injury studies
BBB/tight junction	EJ1514520	Human Zonula Occludens Protein 1 (ZO-1) ELISA Kit	BioReagent	Detection of ZO-1 to evaluate tight junction injury in BBB disruption
BBB/tight junction	EJ1512201	Rat Tight Junction Protein 1 (ZO-1) ELISA Kit	BioReagent	Detection of ZO-1 in rat TBI models
BBB/tight junction	EJ1513011	Mouse Zonula Occludens-1 (ZO-1) ELISA Kit	BioReagent	Detection of ZO-1 in mouse TBI models
BBB/tight junction	Ab119129	Recombinant Occludin Antibody	Recombinant, ExactAb™, Validated, See COA	Detection of Occludin expression to evaluate BBB structural integrity
BBB/tight junction	EJ1512200	Rat Occludin(Occludin) ELISA Kit	BioReagent	Detection of Occludin in rat samples
BBB/tight junction	EJ1513010	Mouse Occludin (Occludin) ELISA Kit	BioReagent	Detection of Occludin in mouse samples
BBB/tight junction	Ab096723	Claudin 5 Antibody	ExactAb™, Validated, 1.0 mg/mL	Detection of Claudin-5 to evaluate brain endothelial barrier integrity

8 Common Research Questions and Result Interpretation

8.1 Why should TBI not be evaluated only by imaging changes?

Some cases of mild TBI or concussion may lack obvious structural imaging abnormalities, but axonal injury, metabolic disturbance, and neuroinflammation may still exist. Imaging is more suitable for showing macroscopic structural injury, while biomarkers and functional assays can supplement information on molecular and cellular injury.

8.2 Why is axonal injury important in TBI?

Axonal fiber tracts are long and sensitive to rotational and shearing forces. Axonal injury disrupts information connectivity between brain regions. Even if neuronal cell bodies do not die immediately, declines in cognition, attention, memory, and reaction speed may occur. Indicators such as NfL, Tau, and APP help evaluate axonal injury.

8.3 What is the difference between GFAP and UCH-L1?

GFAP mainly reflects astrocyte injury and glial responses, whereas UCH-L1 mainly reflects neuronal injury. Combined use of the two can evaluate TBI from both glial and neuronal dimensions, but results still need to be interpreted together with sampling time, injury type, and other detection indicators.

8.4 Why cannot S100B be used alone as a specific marker?

Although S100B is sensitive to brain injury, it may also be affected by peripheral tissue injury, changes in blood-brain barrier permeability, and sample background. Therefore, S100B is more suitable for interpretation together with GFAP, UCH-L1, NfL, and other indicators, rather than as a standalone basis for determining brain injury type.

8.5 Why is NfL suitable for axonal injury research?

NfL is an axonal cytoskeletal protein and can be released into cerebrospinal fluid and blood after axonal injury. Because diffuse axonal injury is an important pathological type of TBI, NfL can be used to reflect axonal injury burden in the acute, subacute, and even chronic phases.

8.6 Is the inflammatory response in TBI always harmful?

Not necessarily. Early inflammation can clear necrotic tissue and initiate repair, but sustained or excessive inflammation aggravates neuronal injury, blood-brain barrier disruption, and cerebral edema. In research, inflammatory effects should be analyzed according to time point and cell type, rather than simply equating increased inflammatory markers with aggravated injury.

8.7 Why is multi-indicator evaluation needed in TBI?

TBI simultaneously involves neurons, axons, glial cells, blood vessels, and the immune system. A single indicator reflects only one pathological aspect, while combined indicators can more completely explain injury type, injury stage, and recovery trend. A more reasonable evaluation system should include histology, molecular biomarkers, blood-brain barrier status, inflammation, oxidative stress, and behavioral function.

The core feature of traumatic brain injury is the superimposition of primary mechanical injury and secondary molecular cascades. Axonal injury, neuronal injury, glial cell responses, blood-brain barrier disruption, oxidative stress, and neuroinflammation jointly determine pathological progression and functional outcomes after TBI. Biomarkers such as GFAP, UCH-L1, S100B, NfL, and Tau provide tools for analyzing TBI pathology from the perspectives of cellular origin and injury type, but more reliable interpretation still depends on multi-indicator, multi-time-point, and multi-level evaluation systems.

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