Long-term functional outcome following transient middle cerebral artery occlusion in the rat: Correlation between brain damage and behavioral impairment.

Abstract

The assessment of both histological and functional long-term outcomes after cerebral ischemia is increasingly recommended for preclinical studies. Whereas correlations between behavioral impairments and primary ischemic lesion are documented, little is known about their relationships with remote nonischemic regions that undergo secondary degeneration, such as the thalamus. Anesthetized rats were subjected to mild (30 min) or severe (60 min) occlusion of the middle cerebral artery. Two months after ischemia, sensorimotor behavior was assessed according to the neurological score, limb-placing, adhesive-removal, and staircase tests; the final histological lesion was measured after this assessment. Cortical damage was correlated to all transient and long-lasting sensorimotor deficits, whereas striatal lesion was more consistently reflected by the forelimb-placing reflexes and adhesive-removal motor deficits. By contrast, the thalamic atrophy was not correlated to early neurological impairment, but rather to the late sensory deficit at the adhesive-removal test and to the skilled forepaw reaching alteration at the staircase test. This suggests that thalamus contributes, albeit moderately, to the ischemia-induced long-lasting sensorimotor deficits, some of which represent relevant targets for therapeutic interventions.

Combined Therapeutic Strategy Using Erythropoietin and Mesenchymal Stem Cells Potentiates Neurogenesis after Transient Focal Cerebral Ischemia in Rats

“…Interestingly, measurements of the rat's performances in the neurological score were correlated with the volumes of lesion assessed on day 3 (r = 0.586, P < 0.001) and on day 16 (r = 0.574, P < 0.001). These results indicate that neurologic scoring is a reliable and sensitive measure, representative of the severity of ischemia (Freret et al, 2006a). In the limb placing test, results similar to the neurological score were observed.…”

“…Thus, these two tests, previously validated in this model of ischemia by Freret et al (2006a), were performed for 3 weeks after cerebral ischemia.…”

MRI Susceptibility Changes Suggestive of Iron Deposition in the Thalamus after Ischemic Stroke

“…Multiple studies have demonstrated secondary damage in the ipsilateral thalamus as the result of neuronal loss and retrograde and anterograde fiber degeneration [15][16][17][18][20][21][22][23][24] . These axonal tracts link the thalamus to other structures functioning as pathways for cerebral iron transport.…”

“…In other ROIs, no difference was found between patients and controls. No associa-In ischemic stroke, secondary changes in the ipsilateral thalamus outside the infarcted area have been demonstrated by several experimental and clinical studies [15][16][17][18][19][20][21][22][23][24] . A study in rats demonstrated hypointense areas in the thalamus after middle cerebral artery (MCA) occlusion on T2 * -w images which correlated with neuronal loss and iron deposition on histologic investigation [19] .…”

Improvements of the Stroke Model Guidelines Animal body weight and long-term functional concerns

“…neurological score (Bederson et al 1986), limb placing test (De Ryck et al 1989), chimney test, cylinder test (Bouet et al 2007)) -those tests would be mostly useful to assess acute phase after stroke, basically from 1 to 7 days) to more complex ones assessing both sensory and motor functions (i.e. adhesive removal , rotarod or staircase (Bouet et al 2007;Freret et al 2009;Freret et al 2006;Grabowski et al 1993;Modo et al 2000;Rogers et al 1997), which are conversely more relevant for long-term phase). Similarly, the memory tests have been developed to investigate cognitive functions (i.e.…”