scholarly journals Sex differences in recovery of motor function in a rhesus monkey model of cortical injury

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Karen R. Bottenfield ◽  
Bethany G. E. Bowley ◽  
Monica A. Pessina ◽  
Maria Medalla ◽  
Douglas L. Rosene ◽  
...  

Abstract Background Stroke disproportionately affects men and women, with women over 65 years experiencing increased severity of impairment and higher mortality rates than men. Human studies have explored risk factors that contribute to these differences, but additional research is needed to investigate how sex differences affect functional recovery and hence the severity of impairment. In the present study, we used our rhesus monkey model of cortical injury and fine motor impairment to compare sex differences in the rate and degree of motor recovery following this injury. Methods Aged male and female rhesus monkeys were trained on a task of fine motor function of the hand before undergoing surgery to produce a cortical lesion limited to the hand area representation of the primary motor cortex. Post-operative testing began two weeks after the surgery and continued for 12 weeks. All trials were video recorded and latency to retrieve a reward was quantitatively measured to assess the trajectory of post-operative response latency and grasp pattern compared to pre-operative levels. Results Postmortem analysis showed no differences in lesion volume between male and female monkeys. However, female monkeys returned to their pre-operative latency and grasp patterns significantly faster than males. Conclusions These findings demonstrate the need for additional studies to further investigate the role of estrogens and other sex hormones that may differentially affect recovery outcomes in the primate brain.

2021 ◽  
Author(s):  
Karen Renee Bottenfield ◽  
Bethany Bowley ◽  
Monica Pessina ◽  
Maria Medalla ◽  
Douglas Rosene ◽  
...  

Abstract Background: Stroke disproportionately affects men and women, with women over 65 experiencing increased severity of impairment and higher mortality rates than men. Human studies have explored risk factors that contribute to these differences, but additional research is needed to investigate how sex differences affect functional recovery and hence the severity of impairment. In the present study, we used our non-human primate model of cortical injury and fine motor impairment to compare sex differences in the rate and degree of motor recovery following this injury. Methods: Aged male and female rhesus monkeys were trained on a task of fine motor function of the hand before undergoing surgery to produce a cortical lesion limited to the hand area representation of the primary motor cortex. Post-operative testing began two weeks after the damage and continued for 12 weeks. All trials were video recorded and latency to retrieve a reward was quantitatively measured to assess the trajectory of post-operative response latency and grasp pattern compared to pre-operative levels. Results: Postmortem analysis showed no differences in lesion volume between male and female. However, females returned to their pre-operative latency and grasp patterns significantly faster than males. To further investigate this finding, we also performed a correlation analyses comparing pre-operative estrogen levels in the females with all measures of recovery. No significant relationship was found. Conclusions: These findings demonstrate the need for additional studies to further investigate the role of estrogen and other sex hormones that may differentially affect recovery outcomes in the primate brain.


2021 ◽  
pp. svn-2020-000834
Author(s):  
Koteswara Rao Nalamolu ◽  
Bharath Chelluboina ◽  
Casimir A Fornal ◽  
Siva Reddy Challa ◽  
David M Pinson ◽  
...  

Background and purposeThe therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial. Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells (MSC) in a rodent stroke model. We hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females, despite any apparent sex differences in post stroke brain injury.MethodsTransient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery. Following the procedure, male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling. Additional groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests (Modified Neurological Severity Score assessment, adhesive tape removal, beam walk and rotarod). The tests were administered at regular intervals (at days 1, 3, 5, 7 and 14) after reperfusion to determine the time course of neurological and functional recovery after stroke.ResultsThe infarct volume and extent of swelling of the ischaemic brain were similar in males and females. Despite similar pathological stroke lesions, the clinical manifestations of stroke were more pronounced in males than females, as indicated by the neurological scores and other tests. MSC treatment significantly improved the recovery of sensory and motor function in both sexes, and it demonstrated efficacy in both moderate stroke (females) and severe stroke (males).ConclusionsDespite sex differences in the severity of post stroke outcomes, MSC treatment promoted the recovery of sensory and motor function in male and female rats, suggesting that it may be a promising treatment for stroke.


2018 ◽  
Vol 35 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Tara L. Moore ◽  
Bethany G. E. Bowley ◽  
Penny L. Shultz ◽  
Samantha M. Calderazzo ◽  
Eli J. Shobin ◽  
...  

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Monica A Pessina ◽  
Bethany G Bowley ◽  
Maria Medalla ◽  
Douglas L Rosene ◽  
Tara L Moore

Curcumin is a primary component of the spice turmeric, and is a potent anti-inflammatory and anti-oxidant compound. In rodent models of brain damage from stroke or trauma, curcumin acts primarily on microglia and astrocytes to inhibit pro-inflammatory signaling pathways and to reduce inflammation and levels of reactive oxygen species (ROS). Further, rats with cortical injury treated with curcumin have smaller lesions and fewer neurological impairments than those treated with vehicle. However, it is not clear whether curcumin exerts the same biological effect in primate brains as in rodent brains, and the effects of curcumin have not yet been extensively tested in monkey models of brain injury. Data from our laboratory has demonstrated that curcumin enhances spatial working memory and motor function in normal aging rhesus monkeys given daily doses of dietary curcumin over two years. The question remains as to whether chronic dietary curcumin can enhance neuroprotection and dampen or ameliorate functional motor deficits after cortical injury. Thus, we administered curcumin to adult, male rhesus monkeys daily for two weeks prior to and 12 weeks following induced cortical injury to the hand-representation of primary motor cortex (M1). Monkeys given daily treatment with oral doses of curcumin, but not those given vehicle, demonstrated significantly enhanced recovery of function in terms of time to retrieve a food reward on our hand dexterity task (HDT). In addition, treated monkeys returned to pre-injury finger-thumb grasp patterns on the HDT, while monkeys that received vehicle developed a compensatory whole hand grasp pattern and never returned to pre-injury grasp. These findings provide evidence that the anti-inflammatory compound, curcumin, is an effective treatment for facilitating recovery of function following cortical injury. Studies investigating the effect of curcumin on the microglia and astrocytes in the brains from these monkeys will provide evidence of the role of curcumin in reducing inflammation and ROS following injury.


2019 ◽  
Vol 37 (4) ◽  
pp. 347-362 ◽  
Author(s):  
T.L. Moore ◽  
B.G.E. Bowley ◽  
M.A. Pessina ◽  
S.M. Calderazzo ◽  
M. Medalla ◽  
...  

2016 ◽  
Vol 34 (5) ◽  
pp. 827-848 ◽  
Author(s):  
Tara L. Moore ◽  
Monica A. Pessina ◽  
Seth P. Finklestein ◽  
Ronald J. Killiany ◽  
Bethany Bowley ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kelly M. Scheulin ◽  
Brian J. Jurgielewicz ◽  
Samantha E. Spellicy ◽  
Elizabeth S. Waters ◽  
Emily W. Baker ◽  
...  

AbstractHarnessing the maximum diagnostic potential of magnetic resonance imaging (MRI) by including stroke lesion location in relation to specific structures that are associated with particular functions will likely increase the potential to predict functional deficit type, severity, and recovery in stroke patients. This exploratory study aims to identify key structures lesioned by a middle cerebral artery occlusion (MCAO) that impact stroke recovery and to strengthen the predictive capacity of neuroimaging techniques that characterize stroke outcomes in a translational porcine model. Clinically relevant MRI measures showed significant lesion volumes, midline shifts, and decreased white matter integrity post-MCAO. Using a pig brain atlas, damaged brain structures included the insular cortex, somatosensory cortices, temporal gyri, claustrum, and visual cortices, among others. MCAO resulted in severely impaired spatiotemporal gait parameters, decreased voluntary movement in open field testing, and higher modified Rankin Scale scores at acute timepoints. Pearson correlation analyses at acute timepoints between standard MRI metrics (e.g., lesion volume) and functional outcomes displayed moderate R values to functional gait outcomes. Moreover, Pearson correlation analyses showed higher R values between functional gait deficits and increased lesioning of structures associated with motor function, such as the putamen, globus pallidus, and primary somatosensory cortex. This correlation analysis approach helped identify neuroanatomical structures predictive of stroke outcomes and may lead to the translation of this topological analysis approach from preclinical stroke assessment to a clinical biomarker.


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