Hostname: page-component-586b7cd67f-2brh9 Total loading time: 0 Render date: 2024-11-24T06:27:01.875Z Has data issue: false hasContentIssue false
  • English
  • Français

Moderate hypothermia, but not calpain inhibitor 2, attenuates the proteolysis of microtubule-associated protein 2 in the hippocampus following traumatic brain injury in rats

Published online by Cambridge University Press:  13 April 2005

Y. Haranishi ,
R. Kawata ,
S. Fukuda ,
T. Kiyoshima ,
Y. Morimoto ,
M. Matsumoto  and
T. Sakabe
Y. Haranishi
Affiliation:
Yamaguchi University School of Medicine, Department of Anesthesiology-Resuscitology, Yamaguchi, Japan
R. Kawata
Affiliation:
Yamaguchi University School of Medicine, Department of Anesthesiology-Resuscitology, Yamaguchi, Japan
S. Fukuda
Affiliation:
Yamaguchi University School of Medicine, Department of Anesthesiology-Resuscitology, Yamaguchi, Japan
T. Kiyoshima
Affiliation:
Yamaguchi University School of Medicine, Department of Anesthesiology-Resuscitology, Yamaguchi, Japan
Y. Morimoto
Affiliation:
Yamaguchi University School of Medicine, Department of Anesthesiology-Resuscitology, Yamaguchi, Japan
M. Matsumoto
Affiliation:
Yamaguchi University School of Medicine, Department of Anesthesiology-Resuscitology, Yamaguchi, Japan
T. Sakabe
Affiliation:
Yamaguchi University School of Medicine, Department of Anesthesiology-Resuscitology, Yamaguchi, Japan
Get access

Abstract

Summary

Background and objective: The degradation of the cytoskeletal protein microtubule-associated protein 2 (MAP2), by calpain has been known to occur following traumatic brain injury. We examined the therapeutic potential of calpain inhibitor 2, compared with that of moderate hypothermia in traumatic brain injury produced by weight drop in rats.

Methods: An inhibitor treated group (n = 8) received calpain inhibitor 2 intravenously (i.v.) for 5 min before and for 6 h after injury (total 2 μmol); a hypothermic (HT) group (n = 8) was maintained at 30°C (temporalis muscle temperature) for 45 min prior to and 60 min after injury; an untreated (UT) group (n = 8) received an infusion of inactive vehicle. Eight rats (sham group) underwent surgery without brain injury. Histopathological (haematoxylin and eosin staining) and MAP2 (immunohistchemistry and western blotting) evaluations were performed at 6 h after injury.

Results: Ipsilateral cortical damage was marked in the injured groups. In the hippocampus, marked pyramidal neuronal damage was observed in the UT and calpain inhibitor treated (CI) groups, while these neurons were better preserved in the HT group. The hippocampal MAP2 levels in the UT, CI and HT groups were significantly decreased to 13 ± 9%, 28 ± 33% and 62 ± 25% of the sham control, respectively. MAP2 concentration in the HT group was significantly higher than in UT and CI groups (P < 0.05).

Conclusion: The results suggest that moderate hypothermia, but not calpain inhibitor 2 with the tested regime, attenuates cytoskeletal damage in the ipsilateral hippocampus at 6 h after traumatic brain injury.

Keywords

BRAIN INJURIES, traumatic, acute, neuroprotectionCALPAIN INHIBITORSHYPOTHERMIA
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 22 , Issue 2 , February 2005 , pp. 140 - 147
Copyright
2005 European Society of Anaesthesiology

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

McIntosh TK, Juhler M, Wieloch T. Novel pharmacologic strategies in the treatment of experimental traumatic brain injury: 1998. J Neurotrauma 1998; 15: 731–769.Google Scholar
Teasdale GM, Graham DI. Craniocerebral trauma: protection and retrieval of the neuronal population after injury. Neurosurgery 1998; 43: 723–738.Google Scholar
Siesjo BK. Basic mechanisms of traumatic brain injury. Ann Emerg Med June 1993; 22: 959–969.Google Scholar
Kampfl A, Posmantur RM, Zhao X, et al. Mechanisms of calpain proteolysis following traumatic brain injury: implications for pathology and therapy: a review and update. J Neurotrauma 1997; 14: 121–134.Google Scholar
Taft WC, Yang K, Dixon CE, Hayes RL. Microtubule-associated protein 2 levels decrease in hippocampus following traumatic brain injury. J Neurotrauma 1992; 9: 281–290.Google Scholar
Posmantur RM, Kampfl BA, Liu SJ, et al. Cytoskeletal derangements of cortical neuronal processes three hours after traumatic brain injury in rats: an immunofluorescence study. J Neuropathol Exp Neurol 1996; 55: 68–80.Google Scholar
Newcomb JK, Kampfl A, Posmantur RM, et al. Immunohistochemical study of calpain-mediated breakdown products to α-spectrin following controlled cortical impact injury in the rat. J Neurotrauma 1997; 14: 369–383.Google Scholar
Hicks R, Smith D, McIntosh TK. Temporal response and effects of excitatory amino acid antagonism on microtubule-associated protein 2 immunoreactivity following experimental brain injury in rats. Brain Res 1995; 678: 151–160.Google Scholar
Johnson GV, Litersky JM, Jope RS, et al. Degradation of microtubule-associated protein 2 and brain spectrin by calpain: a comparative study. J Neurochem 1991; 56: 1630–1638.Google Scholar
Saatman KE, Murai H, Bartus RT, et al. Calpain inhibitor AK295 attenuates motor and cognitive deficits following experimental brain injury in the rat. Proc Natl Acad Sci 1996; 93: 3428–3433.Google Scholar
Posmantur R, Kampfl A, Siman R, et al. A calpain inhibitor attenuates cortical cytoskeletal protein loss after experimental traumatic brain injury in the rat. Neuroscience 1997; 77: 875–888.Google Scholar
Kupina KC, Nath R, Bernath EE, et al. The novel calpain inhibitor SJA6017 improves functional outcome after delayed administration in a mouse model of diffuse brain injury. J Neurotrauma 2001; 18: 1229–1240.Google Scholar
Clark RS, Kochanek PM, Marion DW, et al. Mild posttraumatic hypothermia reduces mortality after severe controlled cortical impact in rats. J Cereb Blood Flow Metab 1996; 16: 253–261.Google Scholar
Taft WC, Yang K, Dixon E, et al. Hypothermia attenuates the loss of hippocampal microtubule-associated protein 2 (MAP2) following traumatic brain injury. J Cereb Blood Flow Metab 1993; 13: 796–802.Google Scholar
Fukuda S, Harada K, Kunimatsu M, et al. Postischemic reperfusion induces α-Fodrin proteolysis by m-calpain in the synaptosome and nucleus in rat brain. J Neurochem 1998; 70: 2526–2532.Google Scholar
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding. Anal Biochem 1976; 72: 248–254.Google Scholar
Tucker RP. The roles of microtubule-associated proteins in brain morphogenesis: a review. Brain Res 1990; 15: 101–120.Google Scholar
Zhao X, Posmantur R, Kampfl A, et al. Subcellular localization and duration of μ-calpain and m-calpain activity after traumatic brain injury in the rat: a case in zymography study. J Cereb Blood Flow Metab 1998; 18: 161–167.Google Scholar
Feeney DM, Boyeson MG, Linn RT, et al. Responses to cortical injury: I. Methodology and local effects of contusions in the rat. Brain Res 1981; 211: 67–77.Google Scholar
Katoh H, Shima K, Nawashiro H, et al. The effect of MK-801 on extracellular neuroactive amino acids in hippocampus after closed head injury followed by hypoxia in rats. Brain Res 1997; 758: 153–162.Google Scholar
Kirino T. Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 1982; 239: 57–69.Google Scholar
Saatman KE, Zhang C, Bartus RT, McIntosh TK. Behavioral efficacy of posttraumatic calpain inhibition is not accompanied by reduced spectrin proteolysis, cortical lesion, or apoptosis. J Cereb Blood Flow Metab 2000; 20: 66–73.Google Scholar
Germano A, Costa C, DeFord SM, et al. Systemic administration of a calpain inhibitor reduces behavioral deficits and blood–brain barrier permeability changes after experimental subarachnoid hemorrhage in the rat. J Neurotrauma 2002; 19: 887–896.Google Scholar
Marion DW, Penrod LE, Kelsey SF, et al. Treatment of traumatic brain injury with moderate hypothermia. New Engl J Med 1997; 336: 540–546.Google Scholar
Clifton GL, Miller ER, Sung CC, et al. Lack of effect of induction of hypothermia after acute brain injury. New Engl J Med 2001; 344: 556–563.Google Scholar
Globus MYT, Alonso O, Dietrich WD, et al. Glutamate release and free radical production following brain injury: effects of posttraumatic hypothermia. J Neurochem 1995; 65: 1704–1711.Google Scholar
Jiang JY, Lyeth BG, Kapasi MZ, et al. Moderate hypothermia reduces blood–brain barrier disruption following traumatic brain injury in the rat. Acta Neuropathol 1992; 84: 495–500.Google Scholar
Bernard SA, Buist M. Induced hypothermia in critical care medicine: a review. Crit Care Med 2003; 31: 2041–2051.Google Scholar