Skip to main content
Log in

Neuronal damage, glial response and cerebral metabolism after hypothermic forebrain ischemia in the rat

  • Regular Papers
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

We investigated the effect of 30°C whole body hypothermia on neuronal injury, astroglial reactivity and intracellular pH in rats subjected to 15 min of forebrain ischemia. Experimental groups included: (1) normothermic ischemia (n=8), ischemia induced under 37°C body temperature, (2) hypothermic ischemia (n=6), ischemia induced under 30°C body temperature. Cerebral intracellular pH was measured using in vivo 31P NMR spectroscopy over 7 days. Neuronal injury and astrocytic reactivity were evaluated using hematoxylin and eosin staining, and immunoreactivity to glial fibrillary acidic protein, respectively. Normothermic animals revealed significant alkalosis (P<0.01) at 48 h after ischemia compared to the pre-ischemic value. No significant intracellular pH change was detected after ischemia in the hypothermic group. Ischemic neuronal injury was prevented in the hypothermic animals, compared to the severe neuronal injury found in the normothermic animals (P<0.01). The marked astrocytosis of normothermic animals was significantly inhibited in the hypothermic animals (P<0.01). Our data indicate, that hypothermia significantly inhibits neuronal injury as well as post-ischemic alkalois and astrocytosis, induced by 15 min of forebrain ischemia in the rat.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Baker AJ, Zornow MH, Grafe MR, Scheller MS, Skilling SR, Smullin DH, Larson AA (1991) Hypothermia prevents ischemia-induced increases in hippocampal glycine concentrations in rabbits. Stroke 22:666–673

    Google Scholar 

  2. Benveniste H, Drejer J, Schousboe A, Diemer NH (1984) Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem 43:1369–1374

    Google Scholar 

  3. Boris-Moller F, Smith ML, Siesjö BK (1989) Effects of hypothermia on ischemic brain damage: a comparison between pre-ischemic and post-ischemic cooling. Neurosci Res Commun 5:87–94

    Google Scholar 

  4. Busto R, Dietrich WD, Globus MYT, Ginsberg MD (1989) Post-ischemic moderate hypothermia inhibits CA1 hippocampal ischemic neuronal injury. Neurosci Lett 101:299–304

    Google Scholar 

  5. Busto R, Globus MYT, Dietrich WD, Martinez E, Valdes I, Ginsberg MD (1989) Effect of mild hypothermia on ischemiainduced release of neurotransmitters and free fatty acids in the rat brain. Stroke 20:904–910

    Google Scholar 

  6. Chen H, Chopp M, Vande Linde AMQ, Dereski MO, Garcia JH, Welch KMA (1992) The effects of post-ischemic hypothermia on the neuronal injury and brain metabolism after forebrain ischemia in the rat. J Neurol Sci 191–198

  7. Chesler M, Kraig RP (1989) Intracellular pH transients of mammalian astrocytes. J Neurosci 9:2011–2019

    Google Scholar 

  8. Chopp M, Knight R, Tidwell CD, Helpern JA, Brown E, Welch KMA (1989) The metabolic effects of mild hypothermia on global cerebral ischemia and recirculation in the cat comparison to normothermia and hyperthermia. J Cereb Blood Flow Metab 9:141–148

    Google Scholar 

  9. Chopp M, Chen H, Vande Linde AMQ, Brown E, Welch KMA (1990) Time course of post-ischemic intracellular alkalosis reflects the duration of ischemia. J Cereb Blood Flow Metab 10:860–865

    Google Scholar 

  10. Chopp M, Vande Linde AMQ, Chen H, Knight R, Helpern JA, Welch KMA (1990) Chronic cerebral intracellular alkalosis following forebrain ischemic insult in rats. Stroke 21:463–466

    Google Scholar 

  11. Chopp M, Chen H, Dereski MO, Garcia JH (1991) Mild hypothermic intervention after graded ischemic stress in rats. Stroke 22:37–43

    Google Scholar 

  12. Currie DN, Kelly JS (1981) Glial versus neuronal uptake of glutamate. J Exp Biol 95:181–193

    Google Scholar 

  13. DeLeo J, Toth L, Schubert P, Rudolphi K, Kreutzberg GW (1987) Ischemia-induced neuronal cell death, calcium accumulation, and glial response in the hippocampus of the mongolian gerbil and protection by propentofylline (HWA 285). J Cereb Blood Flow Metab 7:745–751

    Google Scholar 

  14. Duffy PE (1983) Astrocytes: normal, reactive, and neoplastic. Raven Press, New York, pp 39–44

    Google Scholar 

  15. Eng LF (1988) Regulation of glial intermediate filaments in astrogliosis. In: Norenberg MD, Hertz L, Schousboe A (eds) The Biochemical Pathology Of Astrocytes. Alan R. Liss, New York, pp 79–90

    Google Scholar 

  16. Giffard RG, Weiss JH, Choi DW (1991) Extracellular alkalosis exacerbates glutamate and NMDA toxicity in cultured cortical cells. J Cereb Blood Flow Metab 11:(S) 112

    Google Scholar 

  17. Henn FA, Goldstein MN, Hamberger A (1974) Uptake of the neurotransmitter candidate glutamate by glial. Nature 249:663–664

    Google Scholar 

  18. Jatz DM, Kimelberg HK (1985) Kinetics and autoradiography of high uptake of serotonin by primary astrocyte cultures. J Neurosci 5:1901–1908

    Google Scholar 

  19. Jorgensen MB, Diemer NH (1982) Selective neuron loss after cerebral ischemia in the rat: possible role of transmitter glutamate. Acta Neurol Scand 66:536–546

    Google Scholar 

  20. Kimelberg HK, Ransom BR (1986) Physiological and pathological aspects of astrocytic swelling. In: Fedoroff S, Vernadakis A (eds) Astrocytes: cell biology and pathology of astrocytes, vol 3. Academic Press, New York, pp 129–166

    Google Scholar 

  21. Kraig RP, Chesler M (1990) Astrocytic acidosis in hyperglycemic and complete ischemia. J Cereb Blood Flow Metab 10:104–114

    Google Scholar 

  22. Mathewson AJ, Berry M (1985) Observations on the astrocyte response to a cerebral stab wound in adult rats. Brain Res 327:61–69

    Google Scholar 

  23. Minamisawa H, Nordstrom C-H, Smith ML, Siesjo BK (1990) The influence of mild body and brain hypothermia on ischemic brain damage. J Cereb Blood Flow Metab 10:365–374

    Google Scholar 

  24. Minamisawa H, Smith ML, Siesjö BK (1990) The effect of mild hyperthermia and hypothermia on brain damage following 5, 10, and 15 minutes of forebrain ischemia. Ann Neurol 28:26–33

    Google Scholar 

  25. Norenberg MD (1983) Immunohistochemistry of glutamine synthetase. In: Hertz L, Kvamme E, McGeer EG, Schousboe A (eds) Glutamine, glutamate, and GABA in the Central Nervous System, Alan R. Liss, New York, pp 95–111

    Google Scholar 

  26. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn, Academic Press, New York

    Google Scholar 

  27. Petito CK, Morgello S, Felix JC, Holden LM (1988) Astrocytes in cerebral ischemia. In: Norenberg MD, Hertz L, Schousboe A (eds) The Biochemical Pathology of Astrocytes. Alan R. Liss, New York, pp 341–349

    Google Scholar 

  28. Petito CK, Morgello S, Felix JC, Lesser ML (1990) The two patterns of reactive astrocytosis in post-ischemic rat brain. J Cereb Blood Flow Metab 10:850–859

    Google Scholar 

  29. Petroff OAC, Prichard JW, Behar KL, Alger JR, den Hollender JA, Schullman RG (1985) Cerebral intracellular pH by 31P NMR spectroscopy. Neurology 35:781–788

    Google Scholar 

  30. Rischke R, Krieglstein J (1991) Post-ischemic neuronal damage causes astroglial activation and increase in local cerebral glucose utilization of rat hippocampus. J Cereb Blood Flow Metab 11:106–113

    Google Scholar 

  31. Smith ML, Auer RN, Siesjö BK (1984) The density and distribution of ischemic brain injury in the rat following 2–10 minutes of forebrain ischemia. Acta Neuropathol (Berl) 64:319–332

    Google Scholar 

  32. Syrota A, Samson Y, Boullais C, Wajnberg P, Loc'h C, Crouzwel C, Maziere B, Soussaline F, Baron JC (1985) Tomographic mapping of brain intracellular pH and extracellular water space on stroke patients. J Cereb Blood Flow Metab 5:358–368

    Google Scholar 

  33. Topp KS, Faddis BT, Vijayan VK (1989) Trauma-induced proliferation of astrocytes in the brains of young and aged rats. Glia 2:201–211

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by NINDS grants NS23393 and NS29463

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, H., Chopp, M., Jiang, Q. et al. Neuronal damage, glial response and cerebral metabolism after hypothermic forebrain ischemia in the rat. Acta Neuropathol 84, 184–189 (1992). https://doi.org/10.1007/BF00311393

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00311393

Key words

Navigation