Experimental and Clinical Neuroprotection: An Update

  • C. Werner
Conference paper
Part of the Yearbook of Intensive Care and Emergency Medicine book series (YEARBOOK, volume 1998)


Cerebral ischemia, and or hypoxia, may occur as a consequence of shock, vascular stenosis or occlusion, vasospasm, neurotrauma, and cardiac arrest. The ischemic/hypoxic insult evokes a cascade of pathophysiologic processes which may consecutively result in neuronal necrosis. The first level of the ischemic cascade is the accumulation of lactic acid due to anaerobic glycolysis. This leads to increased membrane permeability and in turn accumulation of perivascular and intracellular fluids. Since the anaerobic metabolism is insufficient to maintain cellular energy states, the adenosine triphosphate (ATP)-stores deplete and failure of energy-dependent membrane ion pumps occurs. This produces membrane depolarization, increases in excitatory neurotransmitter concentration (i.e., glutamate, aspartate) and activation of NMDA- (N-methyl-D-aspartate), AMPA- (α-amino-3-hydroxy-5-methyl-4-isoxazolpropionate), and voltage dependent Ca++- and Na+-channels. The consecutive massive Ca++ and Na+ influx leads to activation of several catabolic intracellular processes. Ca++ activates lipid peroxidases, proteases, and phospholipases which in turn increase the intracellular concentration of free fatty acids (FFA) and free radicals. Consecutively, membrane degeneration of vascular and cellular structures leads to cellular death.


Cerebral Ischemia Acute Stroke Neurologic Outcome Severe Head Injury Aneurysmal Subarachnoid Hemorrhage 
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© Springer-Verlag Berlin Heidelberg 1998

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  • C. Werner

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