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. 2012 Mar;33(3):619.e9-619.e24.
doi: 10.1016/j.neurobiolaging.2011.02.005. Epub 2011 Apr 1.

Recovery from ischemia in the middle-aged brain: a nonhuman primate model

Tara L Moore  1 , Ronald J Killiany, Monica A Pessina, Mark B Moss, Seth P Finklestein, Douglas L Rosene
Affiliations

Recovery from ischemia in the middle-aged brain: a nonhuman primate model

Tara L Moore et al. Neurobiol Aging. 2012 Mar.

Abstract

Studies of recovery from stroke mainly utilize rodent models and focus primarily on young subjects despite the increased prevalence of stroke with age and the fact that recovery of function is more limited in the aged brain. In the present study, a nonhuman primate model of cortical ischemia was developed to allow the comparison of impairments in young and middle-aged monkeys. Animals were pretrained on a fine motor task of the hand and digits and then underwent a surgical procedure to map and lesion the hand-digit representation in the dominant motor cortex. Animals were retested until performance returned to preoperative levels. To assess the recovery of grasp patterns, performance was videotaped and rated using a scale adapted from human occupational therapy. Results demonstrated that the impaired hand recovers to baseline in young animals in 65-80 days and in middle-aged animals in 130-150 days. However, analysis of grasp patterns revealed that neither group recover preoperative finger thumb grasp patterns, rather they develop compensatory movements.

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Conflict of interest statement

Disclosure statement

There are no conflicts of interest for any author of this manuscript, including financial, personal or other relationships with other people or organizations within 3 years of beginning the work that could inappropriately influence the work.

Animal maintenance and research was conducted both in accordance with the guidelines of the National Institutes of Health Committee on Laboratory Animal Resources and with the procedures approved by the Institutional Animal Use and Care Committee of the Boston University Medical Campus.

Figures

Fig. 1
Fig. 1
Magnified photograph of lateral surface of motor and somatosensory cortices of 3 monkeys (1 young and 2 middle-aged) showing stimulation sites. Black circles represent sites that when stimulated produced a strong response of hand and/or digits and white circles represent sites that when stimulated produced weak or no response of hand and/or digits. Scale bar applies to all 3 maps.
Fig. 2
Fig. 2
(A) Postperfusion photograph of a brain from 1 young animal in this study demonstrating the location and extent of the lesion. (B) Representative thionin-stained coronal section from a young animal showing extent of lesion and pathological changes in region of ischemia.
Fig. 3
Fig. 3
A 3-way repeated measures analysis of variance (ANOVA) revealed no significant group differences with the dominant (A) or nondominant (B) hand for the mean latency to retrieve a food reward from each well for the last 5 days of preoperative training. Error bars represent standard error of the mean.
Fig. 4
Fig. 4
A single multivariate analysis of variance (MANOVA) revealed a significant effect of hand on the number of postoperative days to return to preoperative levels of performance on the wide-deep (WD) (p < 0.02), wide-shallow (WS) (p < 0.002), and narrow-deep (ND) wells (p < 0.04), but not on the narrow-shallow (NS) well (p < 0.26) for the young animals. Error bars represent standard error of the mean. Asterisks indicate a significant difference.
Fig. 5
Fig. 5
A single multivariate analysis of variance (MANOVA) revealed a significant effect of hand on the number of postoperative days to return to preoperative levels of performance on wide-shallow (WS) (p < 0.01), narrow-deep (ND) (p < 0.05), and narrow-shallow (NS) wells (p < 0.03), but not for the wide-deep (WD) well (p < 0.07) for the middle-aged animals. Error bars represent standard error of the mean. Asterisks indicate a significant difference.
Fig. 6
Fig. 6
A single multivariate analysis of variance (MANOVA) revealed a significant effect of group on the number of postoperative days to return to preoperative levels of performance with the impaired hand for the wide-deep (WD) (p < 0.05), wide-shallow (WS) (p < 0.01), narrow-deep (ND) (p < 0.03), and narrow-shallow (NS) wells (p < 0.02). Error bars represent standard error of the mean. Asterisks indicate a significant difference.
Fig. 7
Fig. 7
A single multivariate analysis of variance (MANOVA) revealed a significant effect of group on the number of postoperative days to return to preoperative levels of performance with the intact hand for the wide-shallow (WS) well (p < 0.04). There was no significant effect of group on the number of postoperative days to return to preoperative levels of performance with the intact hand for the wide-deep (WD) (p < 0.08), narrow-deep (ND) (p < 0.24), and narrow-shallow (NS) wells (p < 0.46). Error bars represent standard error of the mean. Asterisks indicate a significant difference.
Fig. 8
Fig. 8
The number of days required to reach criterion for the impaired hand for each monkey was divided into 3 equal blocks (each consisting of 1 third of the total days to return to criterion) and the average rating for each period was determined. A Mann-Whitney U test revealed significant age-related differences on the wide-deep (WD) well for the 2nd (p = 0.05) and 3rd (p = 0.05) time periods (A). Analyses for the other wells showed significant differences on the wide-shallow (WS) well for the 1st (p = 0.05) and 2nd (p = 0.05) time periods (B), the narrow-deep (ND) well for the 1st (p = 0.05) time period (C), and for the narrow-shallow (NS) well for the 2nd (p = 0.05) time period (D). Error bars represent standard error of the mean. Asterisks indicate a significant difference.
Fig. 9
Fig. 9
Mean rating of grasp pattern of the impaired hand across the postoperative testing period (wide-deep, p < 0.02; wide-shallow, p < 0.04; narrow-deep, p < 0.009; narrow-shallow, p < 0.005). Error bars represent standard error of the mean. Asterisks indicate a significant difference.
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