Penumbra region excitability is not enhanced acutely after cerebral ischemia in the in vitro isolated guinea pig brain

Epilepsia. 2012 Mar;53(3):448-58. doi: 10.1111/j.1528-1167.2011.03356.x. Epub 2011 Dec 22.


Purpose: Early seizures are a frequent consequence of stroke. The main goal of the present study is to verify whether anoxic ischemia per se is able to induce early changes in excitability that may be a prelude to the generation of seizures and, ultimately, to epileptogenesis. Excitability changes in the very acute postischemic phase are here analyzed in a new model of ischemia developed in the isolated guinea pig brain preparation.

Methods: Permanent bilateral occlusion of the anterior cerebral arteries (ACAs) was performed in the isolated guinea pig brain maintained in vitro by arterial perfusion. Magnetic resonance imaging and immunohistochemistry were utilized to identify the penumbra and core regions induced by ACA occlusion (ACAo). Slow potentials and evoked responses recorded in olfactory cortices were utilized to evaluate excitability changes in the acute phase after ischemia.

Key findings: ACAo induces a core area located in the shell of the nucleus accumbens and a region of penumbra in the underlying olfactory cortices, where characteristic slow potential shifts, but no reduction of diffusion tensor magnetic resonance (MR) signal and microtubule associated protein 2 (MAP-2) immunostaining (typical of ischemic core) was observed. Recording of responses evoked by low- and high-frequency stimulations of the lateral olfactory tract showed no excitability changes in the early hours that follow ischemia in the olfactory cortical areas supplied by ACAs.

Significance: The absence of early hyperexcitability changes in an isolated whole brain model of ischemia, strongly suggests that brain anoxia per se does not contribute to the generation of early seizures. These findings support the view that blood-borne events (such as hemorrhage and inflammation) may play a major role in early postischemic seizures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Brain / pathology
  • Brain / physiopathology*
  • Brain Infarction / complications
  • Brain Infarction / pathology
  • Brain Infarction / physiopathology*
  • Brain Ischemia / complications
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology*
  • Disease Models, Animal
  • Epilepsy / etiology
  • Epilepsy / pathology
  • Epilepsy / physiopathology*
  • Guinea Pigs
  • Organ Culture Techniques