Long-Lasting Functional Disabilities in Middle-Aged Rats with Small Cerebral Infarcts

Abstract

Recommendations from experts and recently established guidelines on how to improve the face and predictive validity of animal models of stroke have stressed the importance of using older animals and long-term behavioral-functional endpoints rather than relying almost exclusively on acute measures of infarct volume in young animals. The objective of the present study was to determine whether we could produce occlusions in older rats with an acceptable mortality rate and then detect reliable, long-lasting functional deficits. A reversible intraluminar suture middle cerebral artery occlusion (MCAO) procedure was used to produce small infarcts in middle-aged rats. This resulted in an acceptable mortality rate, and robust disabilities were detected in functional assays, although the degree of total tissue loss measured 90 d after MCAO was quite modest. Infarcted animals were functionally impaired relative to sham control animals even 90 d after the occlusions, and when animals were subgrouped based on amount of tissue loss, MCAO animals with only 4% tissue loss exhibited enduring neurological-behavioral impairments relative to sham-operated controls, and the functional impairments in the group with the largest infarcts (20% tissue loss) were more severe than the functional impairments in the rats with 4% tissue loss. These results suggest that this model, using reversible MCAO to produce small infarcts and long-lasting functional-behavioral deficits in older rats, may represent an advance in the relatively higher-throughput modeling of stroke and its recovery in rodents and may be useful in the development and characterization of future stroke therapies.

Functional Recovery in Aged and Young Rats After Embolic Stroke

“…6,14,15,16 Thus, our data demonstrate that aging is an important determinant of outcome after embolic stroke. The different patterns of age associated functional outcome measured by NSS and the adhesive removal test suggests that these outcome measurements target different aspects of functional outcome after ischemia.…”

Formation of Descending Pathways Mediating Cortical Command to Forelimb Motoneurons in Neonatally Hemidecorticated Rats

“…Although less dexterous than the intact forelimb, their reaching and grasping movements with the forelimb contralateral to the lesion were fairly good (Takahashi et al 2009). This is in marked contrast to the poor functional recovery of animals whose sensorimotor cortex (SMC) was lesioned in adulthood (Alaverdashvili et al 2008;Barth and Stanfield 1990;Belayev et al 1996;Bland et al 2000;Chen et al 2002;Emerick et al 2003;D'Amato 1970, 1975;Johansson and Ohlsson 1996;Jolkkonen et al 2000;Lindner et al 2003;Markus et al 2005;Roof et al 2001;Schallert et al 2000;Whishaw and Kolb 1988;Yager et al 2006).…”

Changes in Gene Expression in the Rat Hippocampus after Focal Cerebral Ischemia

“…a relatively high rate of mortality (17% within 24 hrs) 12) and small infarcts (8% hemispheric volume).…”