Spatio-temporal distribution of apoptosis and the modulators thereof following a cortical microinfarct in rat brain

Neurosci Res. 2007 Mar;57(3):354-61. doi: 10.1016/j.neures.2006.11.005. Epub 2006 Dec 11.

Abstract

Two mechanisms of brain cell death coexist, necrosis and apoptosis. We investigated the correlation between the apoptotic index and the expression of apoptosis modulators and stress response in an ultraviolet-induced cortical microinfarct. Adult rat neocortex was exposed to an ultraviolet beam and brains removed at different intervals after injury were paraffin-embedded and processed for TUNEL assay and immunohistochemistry against apoptotic modulators Bax and Bcl-2, and stress protein HSP70. During the 12-72h postirradiation period, apoptotic nuclei decreased from 11% to 4% in the infarcted area whereas only 1.2% of such nuclei was seen in the perilesional area. While Bcl-2 was always negative in the lesion focus, Bax was positive at all survival times, mainly in glial cells. HSP70 was expressed over a broad area of the ipsilateral hemisphere from 3h after brain injury, firstly in neurons and progressively in glial cells and finally in endothelium. At longer survival times, positive cells could be also seen in the contralateral hemisphere. Apoptosis seems to play only a quantitatively modest role in the progression of brain damage in penumbra areas despite the wide expression of pro-apoptotic factors. On the other hand HSP70 appears to be one of the main protective responses to injury stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism*
  • Apoptosis* / physiology
  • Apoptosis* / radiation effects
  • Brain Infarction / metabolism
  • Brain Infarction / physiopathology*
  • Cell Count
  • Cell Survival / physiology
  • Cell Survival / radiation effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiopathology*
  • Cerebral Cortex / radiation effects
  • Disease Models, Animal
  • Female
  • HSP70 Heat-Shock Proteins / metabolism
  • Nerve Degeneration / etiology
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / physiopathology
  • Neuroglia / metabolism
  • Neuroglia / radiation effects
  • Neurons / metabolism
  • Neurons / radiation effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Physiological / etiology
  • Stress, Physiological / metabolism
  • Stress, Physiological / physiopathology*
  • Time Factors
  • Ultraviolet Rays / adverse effects
  • bcl-2-Associated X Protein / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • HSP70 Heat-Shock Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein