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Updated: Aug 14, 2026

A Low Mortality Rat Model to Assess Delayed Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage
07:03

A Low Mortality Rat Model to Assess Delayed Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage

Published on: January 17, 2013

Role of MAPK in chronic cerebral vasospasm

K Aoki1, A Y Zubkov, R E Tibbs

  • 1Department of Neurosurgery, University of Mississippi Medical Center, Jackson 39216-4505, USA.

Life Sciences
|May 15, 2002
PubMed

Insights

p44/42 mitogen-activated protein kinase (MAPK) plays a key role in subarachnoid hemorrhage (SAH)-induced cerebral vasospasm. MEK inhibitor PD98059 effectively reversed this vasospasm in a canine model.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Subarachnoid hemorrhage (SAH) can lead to delayed cerebral vasospasm, a significant cause of morbidity and mortality.
  • The precise molecular mechanisms underlying SAH-induced vasospasm are not fully understood.

Purpose of the Study:

  • To investigate the involvement of p44/42 mitogen-activated protein kinase (MAPK) in canine SAH.
  • To determine if MEK inhibitors can mitigate SAH-induced cerebral vasoconstriction.

Main Methods:

  • A double hemorrhage model of SAH was established in dogs.
  • Basilar artery diameter was measured via angiogram over 7 days.
  • p44/42 MAPK levels were assessed using immunoprecipitation.
  • The effect of MEK inhibitor PD98059 on vasospasm and MAPK levels was evaluated.

Main Results:

  • SAH induced a time-dependent decrease in basilar artery diameter, indicative of vasospasm.
  • p44/42 MAPK levels significantly increased following SAH and remained elevated.
  • PD98059 treatment significantly reduced p44/42 MAPK activation.
  • PD98059 administration significantly reversed vasospasm, increasing residual basilar artery diameter.

Conclusions:

  • p44/42 MAPK signaling is implicated in the pathogenesis of cerebral vasospasm after SAH.
  • MEK inhibitor PD98059 demonstrates therapeutic potential for treating SAH-induced vasospasm.

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