Age-dependent modifications in vascular adhesion molecules and apoptosis after 48-h reperfusion in a rat global cerebral ischemia model

Abstract

Stroke is one of the leading causes of death and permanent disability in the elderly. However, most of the experimental studies on stroke are based on young animals, and we hypothesised that age can substantially affect the stroke response. The two-vessel occlusion model of global ischemia by occluding the common carotid arteries for 15 min at 40 mmHg of blood pressure was carried out in 3-and 18-month-old male Sprague-Dawley rats. The adhesion molecules E-and P-selectin, cell adhesion molecules (CAMs), both intercellular (ICAM-1) and vascular (VCAM-1), as well as glial fibrillary acidic protein (GFAP), and cleaved caspase-3 were measured at 48 h after ischemia in the cerebral cortex and hippocampus using Western blot, qPCR and immunofluorescence techniques. Diametric expression of GFAP and a different morphological pattern of caspase-3 labelling, although no changes in the cell number, were observed in the neurons of young and old animals. Expression of E-selectin and CAMs was also modified in an age-and ischemia/reperfusiondependent manner. The hippocampus and cerebral cortex had similar response patterns for most of the markers studied. Our data suggest that old and young animals present different time-courses of neuroinflammation and apoptosis after ischemic damage. On the other hand, these results suggest that neuroinflammation is dependent on age rather than on the different vulnerability described for the hippocampus and cerebral cortex. These differences should be taken into account in searching for therapeutic targets.

Effect of interplay between age and low-flow duration on neurologic outcomes of extracorporeal cardiopulmonary resuscitation

“…Animal studies have also demonstrated that responses to neurologic injuries after ischemia are different in young and old animals [6]; young and old animals exhibit relatively high levels of hypoxic and apoptotic injury, respectively. A previous study [38] on the pathologic examination of patients with cardiac arrest revealed that the severity of hypoxic ischemic brain injury is correlated with prolonged survival time after cardiac arrest instead of age, hypertension, or diabetes.…”

“…Several studies have shown that prolonged LFDs are significantly associated with poor hospital outcomes for ECPR [3, 4], with an approximate survival rate of only 10–17% if LFDs exceed 60 min. Animal experiments have indicated that old and young animals present different degrees of neuroinflammation and apoptosis reaction after brain ischemic damage [5, 6]. The number of elderly patients being referred for ECMO support when undergoing CPR has increased in recent years [7–10].…”

Global gene expression profile of cerebral ischemia-reperfusion injury in rat MCAO model

“…Specific molecules that bind neutrophils, including CAMs and selectins (ICAM2, ICAM4, ICAM5, VCAM, selectin E, and selectin L), exhibited abnormal expression in our experiment. These genes play an important role in leukocyte infiltration and transmigration [ 19 ]. Gfap is a strong marker of gliosis, and may also serve as a marker of neuroinflammation [ 20 , 21 ].…”

Experimental animal models and inflammatory cellular changes in cerebral ischemic and hemorrhagic stroke

“…In addition, differences between old and young animals have been found in the time-courses of neuroinflammation and apoptosis after ischemic damage, suggesting that neuroinflammation is an age-dependent event rather than a vulnerability of the hippocampus and cerebral cortex. These two factors should be taken into account in searching for therapeutic targets in global cerebral ischemia [120] .…”