Trauma-induced cell swelling in cultured astrocytes

Journal of Neuropathology and Experimental Neurology
A R JayakumarMichael D Norenberg

Abstract

Brain edema and associated increased intracranial pressure are major consequences of traumatic brain injury that account for most early deaths after traumatic brain injury. An important component of brain edema after traumatic brain injury is astrocyte swelling (cytotoxic edema). To examine the pathophysiologic mechanisms of trauma-induced astrocyte swelling, we used an in vitro fluid percussion trauma model. Exposure of cultured rat astrocytes to 5 atm of pressure resulted in significant cell swelling at 1 to 24 hours posttrauma that was maximal at 3 hours. Because oxidative/nitrosative stress, mitochondrial permeability transition (mPT), and mitogen-activated protein kinases (MAPKs) have been implicated in astrocyte swelling in other neurologic conditions, we examined their potential roles in this model. We previously showed increased free radical generation after in vitro trauma and show here that trauma to astrocytes increased the production of nitric oxide. Trauma also induced mPT and increased phosphorylation (activation) of MAPKs (extracellular signal-regulated kinase 1/2, c-Jun-N-terminal kinase, and p38-MAPK); these changes were diminished by antioxidants and the nitric oxide synthase inhibitor N-nitro-l-arginine methy...Continue Reading

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Citations

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