Forebrain ischemia induced by temporary bilateral common carotid occlusion in normotensive rats

https://doi.org/10.1016/0022-510X(89)90098-1Get rights and content

Abstract

Ischemic brain lesions were induced in adult Wistar and Fischer rats by temporary occlusion of the bilateral common carotid artery. The severity of ischemic lesions depended on the duration of carotid occlusion. While 2 h occlusion resulted in 15 deaths among 40 rats and the development of ischemic lesions in 16 of 25 asymptomatic survivors, none died after 0.5 h occlusion and yet 13 of 30 apparently asymptomatic rats had ischemic lesions when examined on day 7. Histological examination combined with immunohistochemistry of autologous albumin for assessing the integrity of the blood-brain barrier (BBB) revealed two distinct lesions: (1) ischemic neural damage with extensive tissue permeation of serum albumin, (2) death of individual neurons sparing other neural elements in the absence of the BBB breakdown. Ischemic neural damage with BBB breakdown was common in animals dying within 48 h after reflow. The lesions without BBB breakdown, on the other hand, were found solely in asymptomatic animals in which groups of severely degenerated neurons were preferentially located in the CA 1 region of the hippocampus, the caudoputamen and deeper layers of the neocortex. The sequential measurements of regional cerebral blood flow (rCBF) in the bilateral hippocampus by the hydrogen clearance method disclosed a steady decrease in rCBF after the occlusion, 51% of the pre-occlusion state at 10 min, 35% at 25 min and 32% at 40 min. The simplicity of procedure could make this model suitable for the study of the pathogenesis of ischemic neuronal damage in a critically low perfusion state.

References (18)

  • M.W. Brightman et al.

    The blood-brain barrier to proteins under normal and pathological conditions

    J. Neurol. Sci.

    (1970)
  • T. Kirino et al.

    Delayed neuronal death in the gerbil hippocampus following ischemia

    Brain Res.

    (1982)
  • J.B. Bederson et al.

    Rat middle cerebral artery occlusion: evaluation of the model and development of a neurological examination

    Stroke

    (1986)
  • S.T. Chen et al.

    A model of focal ischemic stroke in the rat: Reproducible extensive cortical infarction

    Stroke

    (1986)
  • T.F. Doyle et al.

    Estimating the total blood flow from the initial slope of hydrogen washout curves

    Stroke

    (1975)
  • B. Eklöf et al.

    The effect of bilateral carotid artery ligation upon the blood flow and the energy state of the rat brain

    Acta Physiol. Scand.

    (1972)
  • H. Iizuka et al.

    Evolution of tissue damage in compressive spinal cord injury in rats

    J. Neurosurg.

    (1987)
  • Y. Iwasaki et al.

    Evolution of rat forebrain ischemia induced by prolonged common carotid occlusion (abstract)

    J. Neuropath. Exp. Neurol.

    (1987)
  • M. Juhler et al.

    The distribution of immunoglobulin and albumin in the central nervous system in acute experimental allergic encephalomyelitis

    Acta Neurol. Scand.

    (1986)
There are more references available in the full text version of this article.

Cited by (78)

  • Ozagrel a thromboxane A2 synthase inhibitor extenuates endothelial dysfunction, oxidative stress and neuroinflammation in rat model of bilateral common carotid artery occlusion induced vascular dementia

    2021, Vascular Pharmacology
    Citation Excerpt :

    BCCAo is an established and commonly used animal model to induce VaD as a consequence of cerebrovascular hypoperfusion and related abnormalities [39]. Decreased cerebral perfusion; endothelial dysfunction; impairment of learning and memory and neuropathological changes have been reported to be associated with BCCAo [54,57,58]. Impaired blood supply to brain regions during BCCAo is further known to cause severe oxidative stress [59] and produce cholinergic dysfunction [39].

  • Tomentosin inhibit cerebral ischemia/reperfusion induced inflammatory response via TLR4/ NLRP3 signalling pathway – in vivo and in vitro studies

    2020, Biomedicine and Pharmacotherapy
    Citation Excerpt :

    Cerebral ischemia reperfusion (I/R) was performed in rats after orally treating the rats with 25 mg/kg bodyweight (b.wt) and 50 mg/kg b.wt of tomentosin daily for seven consecutive days. The cerebral occlusion was carried as per the previous protocol [32]. The rats were anesthetized with intraperitoneal injection of 1% pentobarbital sodium solution (30 mg/kg) and the skin was exposed through an incision in midline neck.

  • The impact of single and combined PPAR-α and PPAR-γ activation on the neurological outcomes following cerebral ischemia reperfusion

    2020, Life Sciences
    Citation Excerpt :

    The doses were chosen according to previous studies [19–23] and to our preliminary studies. After 14 days of pretreatment the first, sixth, seventh and eighth groups served as sham operated rats pretreated with vehicle, fenofibrate (100 mg/kg/day p.o) pioglitazone (10 mg/kg/day p.o) and fenofibrate (100 mg/kg/day) + pioglitazone (10 mg/kg/day) while, the other groups were subjected to ischemia reperfusion (I/R) injury as previously described [24,25]. Briefly, animals were anaesthetized by intraperitoneal injection of a mixture of ketamine (80 mg/kg) and xylazine (10 mg/kg) and kept over a heating bed.

  • Hydrogen sulfide intoxication induced brain injury and methylene blue

    2020, Neurobiology of Disease
    Citation Excerpt :

    Necrotic lesions also involve the caudate putamen, thalamus as well as amygdala (Sonobe et al., 2015). The piriform cortex, cerebellar Purkinje cell layer and hippocampal (CA1-3 and dentate gyrus) neuronal populations were never affected (Fig. 5), in major contrast to the effects of anoxia-induced brain damage in which the deeper layers of cerebral cortex along with hippocampal and neocortical pyramidal cells, striatal neurons, and Purkinje cells (Brierley and Excell, 1966; Graham et al., 1990; Iwasaki et al., 1989) are affected. The lack of memory deficit during MWM testing could be explained by the absence of hippocampal lesions (Sonobe et al., 2015), while the motor deficit and blindness can be accounted for by lesions affecting the thalamus, the motor or visual cortex as well as subcortical nuclei (Fig. 5).

View all citing articles on Scopus
View full text