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Moderate hypothermia reduces blood-brain barrier disruption following traumatic brain injury in the rat

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Summary

The effects of moderate hypothermia on blood-brain barrier (BBB) permeability and the acute hypertensive response after moderate traumatic brain injury (TBI) in rats were examined. TBI produced increased vascular permeability to endogenous serum albumin (IgG) in normothermic rats (37.5°C) throughout the dorsal cortical gray and white matter as well as in the underlying hippocampi as visualized by immunocytochemical techniques. Vascular permeability was greatly reduced in hypothermic rats cooled to 30°C (brain temperature) prior to injury. In hypothermic rats, albumin immunoreactivity was confined to the gray-white interface between cortex and hippocampi with no involvement of the overlying cortices and greatly reduced involvement of the underlying hippocampi. The acute hypertensive response in normothermic rats peaked at 10 s after TBI (187.3 mm Hg) and returned to baseline within 50 s. In contrast, the peak acute hypertensive response was significantly (P<0.05) reduced in hypothermic rats (154.8 mm Hg, 10 s after TBI) and returned to baseline at 30 s after injury. These results demonstrate that moderate hypothermia greatly reduces endogenous vascular protein-tracer passage into and perhaps through the brain. This reduction may, in part, be related to hypothermia-induced modulation of the systemic blood pressure response to TBI.

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References

  1. Baker AJ, Zornow MH, Grafe MR, Scheller MS, Yaksh TL, Larson AA (1991) Hypothermia prevents ischemia-induced increases in hippocampal glycine concentrations. Satellite Symposium Brain-91: The Role of Neurotransmitters in Brain Injury Key West, Florida. Plenum Publishing Corporation, New York, p 10

    Google Scholar 

  2. Baker H, Lindsey J, Weisbroth S (1979) Selected normative data. In: Baker HJ, Lindsey JR, Weisbroth SH (eds) The laboratory rat, vol 1. academic Press, New York, pp 411–412

    Google Scholar 

  3. Busto R, Dietrich WD, Globus MYT, Valdes I, Scheinber P, Ginsberg MD (1987) Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J Cereb Blood Flow Metab 7:729–738

    Google Scholar 

  4. Busto R, Dietrich WD, Globus MYT, Ginsberg MD (1989) The importance of brain temperature in cerebral ischemic injury. Stroke 20:1113–1114

    Google Scholar 

  5. Busto R, Dietrich WD, Globus MYT, Castella Y, Ginsberg MD (1989) Postischemic moderate hypothermia inhabits CA1 hippocampal ischemic neuronal injury. J Cereb Blood Flow Metab 9 [suppl 1]:266

    Google Scholar 

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

    Google Scholar 

  7. 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 

  8. Chou C-L, Lyeth BG, Jenkins LW, Hayes RL, Povlishock JT (1991) Regional cerebral blood flow changes after traumatic brain injury in the rat. Soc Neurosci Abstr 17:722

    Google Scholar 

  9. Churn SB, Blair RE, Taft WC, Delorenzo RJ (1989) Hypothermia blocks ischemia-induced inhibition of CaM kinase II. Soc Neurosci Abstr 15:360

    Google Scholar 

  10. Clifton GL, Taft WC, Blair RE, Choi SF, DeLorenzo RJ (1989) Conditions for pharmacologic evaluation in the gerbil model of forebrain ischemia. Stroke 20:1545–1552

    Google Scholar 

  11. Clifton GL, Jiang JY, Lyeth BG, Jenkins LW, Hamm RJ, Hayes RL (1991) Marked protection by moderate hypothermia after experimental traumatic brain injury. J Cereb Blood Flow Metab 11:114–121

    Google Scholar 

  12. Cortez SC, McIntosh TK, Noble LJ (1989) Experimental fluid percussion brain injury: vascular disruption and neuronal and glial alterations. Brain Res 482:271–282

    Google Scholar 

  13. Dempsey R, Combs DJ, Maley ME, Cowen DE, Roy MW, Donaldson DL (1987) Moderate hypothermia reduces post-ischemic edema development and leukotriene production. Neurosurgery 21:177–181

    Google Scholar 

  14. DeWitt DS, Jenkins LW, Weir EP, et al (1986) The effects of fluid percussion brain injury on regional and total cerebral blood flow and pial vessel diameter: a combined pial window and microsphere study. J Neurosurg 64:787–794

    Google Scholar 

  15. Dietrich WD, Busto R, Halley M, Valdes I (1990) The importance of brain temperature in alterations of the blood-brain barrier following cerebral ischemia. J Neuropathol Exp Neurol 49:486–497

    Google Scholar 

  16. Dixon CE, Lyeth BG, Povlishock JT, Findling RL, Hamm RJ, Marmarou A, Young HF, Hayes RL (1987) A fluid percussion model of experimental brain injury in the rat. J Neurosurg 67:110–119

    Google Scholar 

  17. Ellis EF, Chao J, Heizer ML (1989) Brain kininogen following experimental brain injury: evidence for a secondary event. J Neurosurg 71:437–442

    Google Scholar 

  18. Ellison MD, Povlishock JT, Hayes RL (1986) Examination of the blood-to brain transfer of α-aminoisobutyric acid horseradish peroxidase: regional alterations in blood-brain barrier function following acute hypertension. J Cereb Blood Flow Metab 6:471–480

    Google Scholar 

  19. Estrada C, Bready J, Berliner J, Cancilla PA (1990) Choline uptake by cerebral capillary endothelial cells in culture. J Neurochem 54:1467–1473

    Google Scholar 

  20. Faden AI, Demediuk P, Panter SS, Vink R (1989) The role of excitatory amino acid and NMDA receptors in traumatic brain injury. Science 244:789–800

    Google Scholar 

  21. Ginsberg MD, Busto R, Castella Y, Valdes I, Loor J (1989) The protective effect of moderate intra-ischemic brain hypothermia is associated with improved postischemic glucose utilization and blood flow. J Cereb Blood Flow Metab 9 [suppl 1]:380

    Google Scholar 

  22. Hayes RL, Jenkins LW, Lyeth BG, Balster RL, Robinson SE, Miller LP, Clifton GL, Young HF (1988) Pretreatment with phencyclidine, an N-methyl-d-aspartate receptor antagonist, attenuates long-term behavioral deficits in the rat produced by traumatic brain injury. J Neurotrauma 5:287–302

    Google Scholar 

  23. Hayes RL, Jenkins LW, Lyeth BG (1991) Neurotransmittermediated mechanisms of traumatic brain injury: acetylcholine and excitatory amino acids. J Neurotrauma 9 [Suppl 1]:173–187

    Google Scholar 

  24. Hoffman WE, Werner C, Baughman VL, Thomas C, Miletich DJ, Albrecht RF (1991) Postischemic treatment with hypothermia improves outcome from incomplete cerebral ischemia in rats. J Neurosurg Anesthesiol 3:34–38

    Google Scholar 

  25. Jenkins LW, Lyeth BG, LeWelt W, Moszynski K, DeWitt DS, Balster RL, Miller LP, Clifton GL, Young HF, Hayer RL (1988) Combined pre-trauma scopolamine and phencyclidine attenuates post-traumatic increased sensitivity to delayed secondary ischemia. J Neurotrauma 5:275–287

    Google Scholar 

  26. Jiang JY, Lyeth BG, Clifton GL, Jenkins LW, Hamm RJ, Hayes RL (1991) Relationship between body and brain temperature in traumatically brain-injured rodents. J Neurosurg 74: 492–496

    Google Scholar 

  27. Johansson B, Li C, Olsson Y, Klatzo I (1970) The effect of acute arterial hypertension on the blood-brain barrier to protein tracers. Acta Neuropathol (Berl) 16:117–124

    Google Scholar 

  28. Krantis A (1983) Hypothermia-induced reduction in the permeation of radiolabelled tracer substances across the blood-brain barrier. Acta Neuropathol (Berl) 60:61–69

    Google Scholar 

  29. Lyeth BG, Dixon CE, Jenkins LW, Hamm RJ, Alberico A, Young HF, Stonnington HH, Hayes RL (1988) Effects of scopolamine treatment on long-term behavioral deficits following concussive brain injury to the rat. Brain Res 452:39–48

    Google Scholar 

  30. Lyeth BG, Jiang JY, Robinson SE, Goo H, Jenkins LW, Hayes RL (1991) Hypothermia blunts acetylcholine increase in CSF in traumatically brain injured rats. Soc Neurosci Abstr 17:165

    Google Scholar 

  31. McIntosh TK, Vink R, Noble L, Yamakami I, Soares H, Faden AL (1989) Traumatic brain injury in the rat: chracterization of a lateral fluid-percussion model. Neuroscience 28:233–244

    Google Scholar 

  32. McIntosh TK, Vink R, Soares H, Hayes RL, Simmon R (1989) Effects of N-methyl-d-aspartate receptor blocker MK-801 on neurologic function after experimental brain injury. J Neurotrauma 6:247–259

    Google Scholar 

  33. Nagy Z, Mathieson G, Huttner I (1979) Opening of tight junctions in cerebral endothelium. II. Effect of pressure-pulse induced acute arterial hypertension. J Comp Neurol 185:579–586

    Google Scholar 

  34. Pardridge WM, Eisenberg J, Yang J (1987) Human blood-brain barrier transferrin receptor. Metabolism 36:892–895

    Google Scholar 

  35. Povlishock JT, Lyeth BG (1989) Traumatically induced blood-brain brain barrier disruption: a conduit for the passage of circulating excitatory neurotransmitters. Soc Neurosci Abstr 15:1113

    Google Scholar 

  36. Povlishock JT, Becker DP, Sullivan HG, Miller JD (1978) Vascular permeability alterations to horseradish peroxidase in experimental brain injury. Brain Res 153:223–239

    Google Scholar 

  37. Rapoport SI (1976) Opening of the blood-brain barrier by acute hypertension. Exp Neurol 52:467–479

    Google Scholar 

  38. Robinson SE, Martin RM, Davis TR, Gyenes CA, Ryland JE, Enters EK (1990) The effect of acetylcholine depletion on behavior following traumatic brain injury. Brain Res 509:41–46

    Google Scholar 

  39. Thompson SM, Masukawa LM, Prince DA (1985) Temperature dependence of intrinsic membrane properties and synaptic potentials in hippocampal CA1 neurons in vitro. J Neurosci 5:817–824

    Google Scholar 

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Authors and Affiliations

  1. Division of Neurosurgery, Department of Surgery, Medical College of Virginia/Virginia Commonwealth University, MCV Station, Box 693, 23298-0693, Richmond, VA, USA

    J. Y. Jiang, B. G. Lyeth & L. W. Jenkins

  2. Department of Anatomy, Medical College of Virginia/Virginia Commonwealth University, MCV Station, Box 693, 23298-0693, Richmond, VA, USA

    M. Z. Kapasi & J. T. Povlishock

Authors
  1. J. Y. Jiang
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  2. B. G. Lyeth
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  3. M. Z. Kapasi
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  4. L. W. Jenkins
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  5. J. T. Povlishock
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Additional information

Supported by Grants NS 12587 (BGL), NS 29469 (JTP), NS 19550 (LWJ) from the National Institutes of Health and Grant H133B80029 (BGL) from the National Institute on Disability and Rehabilitation Research, the U.S. Department of Education

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Jiang, J.Y., Lyeth, B.G., Kapasi, M.Z. et al. Moderate hypothermia reduces blood-brain barrier disruption following traumatic brain injury in the rat. Acta Neuropathol 84, 495–500 (1992). https://doi.org/10.1007/BF00304468

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  • DOI: https://doi.org/10.1007/BF00304468

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