Application of an external physical force also may subject the brain to contact, forces – that is, injury produced when the brain strikes the inner table of the skull, especially the bony ridges and protuberances within and between the anterior and middle cranial fossae.37 In addition to TWS119 in vivo compressive damage to brain tissue caused by forceful brain-skull contacts, local (ie, focal) vascular/hemorrhagic, cytotoxic, and inflammatory injury also

is induced. The combination of inertial forces, contact, forces, and Inhibitors,research,lifescience,medical cellular/metabolic events associated with the application of biomechanical force tends to disrupt, the function (and, as initial injury severity increases, the structure) of a relatively predictable set of brain areas – including, and especially, anterior and ventral

Inhibitors,research,lifescience,medical frontal and temporal areas, cerebral hemispheric white matter, and the upper brain stem/brain stem-diencephalic junction. In light of the neuropsychiatric functions served by these brain structures, TBI therefore also produces a relatively predictable set, of neuropsychiatric disturbances (Table IV). Table IV. Brain areas most vulnerable to traumatic Inhibitors,research,lifescience,medical brain injury, the neuropsychiatric functions in which they are involved, and the neuropsychiatric consequences of injury to these areas. GABA, γ-aminobutyric acid; DA, dopamine; NE, norepinephrine; 5HT, … Although these disturbances in brain-behavior relationships are typical of TBI, the ncurobiological consequences of such injuries vary greatly between patients and even within patients with clinically similar initial TBI severities.29,64 Some, but, not all, individuals with TBI experience overt structural Inhibitors,research,lifescience,medical injury; when structural injury occurs, the locations and severities of those injuries are highly variable, as are the magnitudes and durations of concomitant, local and diffuse cytotoxic disturbances.34,35,59,65 Neurophysiologically, there are at least five hypothetical sets of processes Inhibitors,research,lifescience,medical that contribute to acute alterations of consciousness and/or sensorimotor function; these are

described by Shaw59 as the vascular, reticular, centripetal, pontine cholinergic system, and convulsive hypotheses of concussion. Some of these processes may develop in the absence of disruptions of brain structure, and some elements of these also are quite transient. However, some of these evolve over time after injur}’ and may entail chronic alterations of the function of modulatory cerebral Chlormezanone neurotransmitter systems.60-62 All TBIs involve some, but not, all, of these processes. Unfortunately, presently available clinical neurodiagnostics do not afford comprehensive identification of the entire spectrum of functional and structural consequences of biomcchanically induced neurotrauma at the single-patient level – especially at the mild end of the TBI severity continuum and, at all levels of TBI severity, the microcellular aspects of neuropathophysiology.