Pathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences

Abstract

Summary: Current knowledge regarding the pathophysiology of cerebral ischemia and brain trauma indicates that similar mechanisms contribute to loss of cellular integrity and tissue destruction. Mechanisms of cell damage include excitotoxicity, oxidative stress, free radical production, apoptosis and inflammation. Genetic and gender factors have also been shown to be important mediators of pathomechanisms present in both injury settings. However, the fact that these injuries arise from different types of primary insults leads to diverse cellular vulnerability patterns as well as a spectrum of injury processes. Blunt head trauma produces shear forces that result in primary membrane damage to neuronal cell bodies, white matter structures and vascular beds as well as secondary injury mechanisms. Severe cerebral ischemic insults lead to metabolic stress, ionic perturbations, and a complex cascade of biochemical and molecular events ultimately causing neuronal death. Similarities in the pathogenesis of these cerebral injuries may indicate that therapeutic strategies protective following ischemia may also be beneficial after trauma. This review summarizes and contrasts injury mechanisms after ischemia and trauma and discusses neuroprotective strategies that target both types of injuries.

Increased Intracranial Pressure after Diffuse Traumatic Brain Injury Exacerbates Neuronal Somatic Membrane Poration but not Axonal Injury: Evidence for Primary Intracranial Pressure-Induced Neuronal Perturbation

“…While the majority of research investigating elevated ICP after TBI has focused exclusively on attendant ischemic pathology precipitated by a drastic reduction in CPP with elevated ICP (Marin-Caballos et al, 2005;Li et al, 2010), this study is the first report of posttraumatic ICP-associated pathology generated without concurrent reduction of CPP to levels classically associated with cerebral ischemia (Dennis et al, 2009;Navarro et al, 2012). The absence of homogeneous tissue damage in the neocortex (Bramlett and Dietrich, 2004) coupled with the observation that that fluid percussion injury does not reduce cerebral blood flow to ischemic levels (Yamakami and McIntosh, 1991) also argues against the possibility of ischemic events. Further, the rigorous physiological inclusion criteria implemented in the current study reduce the possibility of introducing variability due to ensuing ischemia.…”

In vivoContributions of BH3-Only Proteins to Neuronal Death Following Seizures, Ischemia, and Traumatic Brain Injury

“…Neuronal death following ischemia and TBI arise from different primary insults, but there are common aspects to their pathophysiology that are also shared with status epilepticus, including glutamate-induced excitotoxicity, oxidative stress, mitochondrial dysfunction, and inflammation (Bramlett and Dietrich, 2004;Liou et al, 2003). Focal cerebral ischemia arises when there is prolonged occlusion of a major artery, whereas in global ischemia cerebral blood flow reduction is brief but complete.…”

“…Indeed, neurologic injury in each condition can be reduced by glutamate receptor antagonists or interrupting the function of apoptosis-associated proteins such as caspases, apoptosis-inducing factor, and proapoptotic genes such as p53 (Liou et al, 2003;Mehta et al, 2007). There are also pathophysiologically distinct components to each insult, for example increased rather than decreased blood supply in status epilepticus as compared with ischemia or TBI, and a direct mechanical component to injury in TBI (Bramlett and Dietrich, 2004).…”

Changes in Autophagy after Traumatic Brain Injury

“…The reason for the difference in the LC3-II level between TBI and HI is unknown, but it is probably because the pathophysiology incurred by TBI is far from identical to that of HI (Siesjo et al, 1995). Traumatic brain injury produces shear forces that primarily damage cell bodies and processes, whereas HI leads to metabolic failure (Bramlett and Dietrich, 2004;Zhu et al, 2006;Chu, 2006).…”

“…Traumatic brain injury (TBI) is a serious and debilitating health problem affecting millions of people each year (http://www.ninds.nih.gov). Traumatic brain injury leads to brain tissue damage and cognitive impairment (Bramlett and Dietrich, 2004). Although remarkable progress has been made in pathophysiology, molecular events after TBI are still incompletely understood.…”