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321,336 Altered phosphorylation of insulin receptor substrate proteins, particularly IRS-1 and IRS-2, is implicated in neuronal insulin resistance, 20,337 which impairs insulins neurotrophic effects, leading to reduced neurite outgrowth and increased vulnerability to injury

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Within four to six hours after ischemia onset, circulating leukocytes adhere to vessel walls and migrate into the brain with subsequent release of additional pro-inflammatory mediators and secondary injury in the penumbra