Post-ischemic hypothermia delayed neutrophil accumulation and microglial activation following transient focal ischemia in rats
Introduction
Concerning the pathophysiology of focal ischemia, it has been demonstrated that the involvement of inflammatory response exacerbates the ischemic injury. Some cellular components of the immune system, neutrophils and microglia in particular, have been reported to play a crucial role. Following ischemia, neutrophils migrate into the tissue and provoke injury by disturbing microcirculation and by releasing toxic substances such as free radicals and proteolytic enzymes (Hallenbeck et al., 1986, Barone et al., 1991, del Zoppo et al., 1991, Schmid-Schonbein, 1994). Similarly, microglia proliferates and becomes activated following ischemia (Banati et al., 1993, Morioka et al., 1993, Kato et al., 1996). This contributes to the tissue injury by phagocytosis and by releasing toxic substances. The suppression of their noxious activities can lead to potential neuroprotection. Recently, several studies have reported the attenuation of the adverse effect of these inflammatory cells in hypothermia; intra-ischemic hypothermia reduced both the accumulation of neutrophils and the infarct volume (Toyoda et al., 1997). Similarly, intra-ischemic hypothermia suppressed the proliferation/activation of microglia and attenuate neuronal cell death (Kumar and Evans, 1997). However, few studies have evaluated the effect of post-ischemic hypothermia on these immune components in the central nervous system. The authors investigated in this study whether, in prolonged post-ischemic hypothermia, (1) the accumulation of neutrophils and/or the activation of microglia is attenuated, or (2) possible change in the activity of these immune components has any influence on the evolution of infarction.
Section snippets
Animal preparation
Total of 80 male Wistar rats (300–350 g in body weight) were employed. Anesthesia was induced with 4.0% halothane and maintained with 1.0–1.5% halothane with a mixture of 70% N2O and 30% O2. Animals received 1 h of left middle cerebral artery occlusion (MCAO) using an intra-luminal suture method. The left common carotid artery, external carotid artery (ECA) and internal carotid artery (ICA) were isolated via a ventral midline incision. A 4-0 nylon monofilament with its tip rounded by heating,
Neutrophils
The number of neutrophils in the ischemic hemisphere was plotted as a function of time and shown in Fig. 1. In the normothermic group, the number of neutrophils was 467.3±172.4, 333.0±207.7, 74.7±16.2 and 40.7±17.8 at days 2, 3, 5 and 7, respectively. In the hypothermic group, the number was 152.3±89.9, 483.0±174.7, 192.3±46.7 and 48.0±14.8 at days 2, 3, 5 and 7, respectively. In the normothermic group, the number of neutrophils reached a peak at 2 days after reperfusion, whereas in the
Discussion
In the progression of focal ischemia, neutrophils play a crucial role by several mechanisms, including the disturbance of microcirculation and the release of free radicals and proteolytic enzymes (Hallenbeck et al., 1986, Barone et al., 1991, del Zoppo et al., 1991, Schmid-Schonbein, 1994). In intra-ischemic hypothermia, it has been reported that the accumulation of neutrophils in the ischemic tissue was attenuated, resulting in the reduction of the infarct volume in rat transient focal
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