Traumatic brain injury (TBI) is defined as a result of a bump, blow or jolt to the head or a penetrating head injury that disrupts the normal function of the brain. This trauma can lead to temporary or permanent impairments of cognitive, physical and psychosocial functions, and an associated diminished or altered state of consciousness 1).
Head impact direction has been identified as an influential risk factor in the risk of traumatic brain injury (TBI) from animal and anatomic research.
Increased risk of incurring a subdural hematoma exists from impacts to the frontal or occipital regions, and parenchymal contusions from impacts to the side of the head. There was no definitive link between impact direction and subarachnoid hemorrhage. In addition, the results indicate that there is a continuum of stresses and strain magnitudes between lesion types when impact location is isolated, with subdural hematoma occurring at lower magnitudes for frontal and occipital region impacts, and contusions lower for impacts to the side.
This hospital data set suggests that there is an effect that impact direction has on TBI depending on the anatomy involved for each particular lesion 2).
After TBI, cerebral vascular endothelial cells play a crucial role in the pathogenesis of inflammation.
Following TBI, various mediators are released which enhance vasogenic and/or cytotoxic brain edema. These include glutamate, lactate, H(+), K(+), Ca(2+), nitric oxide, arachidonic acid and its metabolites, free oxygen radicals, histamine, and kinins. Thus, avoiding cerebral anaerobic metabolism and acidosis is beneficial to control lactate and H(+), but no compound inhibiting mediators/mediator channels showed beneficial results in conducted clinical trials, despite successful experimental studies.
White matter injury is an important contributor to long term motor and cognitive dysfunction after traumatic brain injury. During brain trauma, acceleration, deceleration, torsion, and compression forces often cause direct damage to the axon tracts, and pathways that are triggered by the initial injury can trigger molecular events that result in secondary axon degeneration. White matter injury is often associated with altered mental status, memory deficits, motor or autonomic dysfunction, and contribute to the development of chronic neurodegenerative diseases. The presence and proper functioning of oligodendrocyte precursor cells offer the potential for repair and recovery of injured white matter. The process of the proliferation, maturation of oligodendrocyte precursor cells and their migration to the site of injury to replace injured or lost oligodendrocytes is known as oligodendrogenesis 3).
The neuropathology of traumatic brain injury (TBI) from various causes in humans is not as yet fully understood.
Penetrating head injury and closed head injury (CHI) that are moderate to severe are more likely than mild TBI (mTBI) to cause gross disruption of the cerebral vasculature. Axonal injury is classically exhibited as diffuse axonal injury (DAI) in severe to moderate CHI. Diffuse axonal injury is also prevalent in penetrating head injury (PHI). It is less so in mTBI. There may be a unique pattern of periventricular axonal injury in explosive blast mTBI. Neuronal injury is more prevalent in PHI and moderate to severe CHI than mTBI. Astrocyte and microglial activation and proliferation are found in all forms of animal TBI models and in severe to moderate TBI in humans. Their activation in mTBI in the human brain has not yet been studied 4).
Due to the marked heterogeneity of human traumatic brain injury (TBI), none of the available animal model can reproduce the entire spectrum of TBI, especially mild focal TBI.
A stereotaxic coupled weight drop device was designed. Principle arm of device carries up to 500g weights which their force was conveyed to animal skull through a thin nail like metal tip. To determine the optimal configuration of the device to induce mild TBI, six different trials were designed. The optimal configuration of the instrument was used for evaluation of behavioral, histopathological and molecular changes of mild TBI.
Neurologic and motor coordination deficits observed sharply within 24h post injury period. Histological studies revealed a remarkable increase in the number of dark neurons in trauma site. TBI increased the expression of apoptotic proteins, Bax, BCl2 and cleaved caspase-3 in the hippocampus.
This device is capable to produce variable severity of TBI from mild to severe. The main advantage of the new TBI model is induction of mild local unilateral brain injury instead of traumatization of the whole brain. This model does not require craniotomy for induction of brain injury.
This novel animal TBI model mimics human mild focal brain injury. This model is suitable for evaluation of pathophysiology as well as screening of new therapies for mild TBI 5).
Brain Injury Association of Tasmania http://www.biat.org.au
Brain Injury Network of South Australia http://www.binsa.org
Brain Injury Association of NSW http://www.biansw.org.au