Abstract
Persistent neurobehavioral deficits and brain changes need validation for brain restoration. Two hours middle cerebral artery occlusion (tMCAO) or sham surgery was performed in male Sprague-Dawley rats. Neurobehavioral and cognitive deficits were measured over 10 weeks included: (1) sensory, motor, beam balance, reflex/abnormal responses, hindlimb placement, forepaw foot fault and cylinder placement tests, and (2) complex active place avoidance learning (APA) and simple passive avoidance retention (PA). Electroretinogram (ERG), hemispheric loss (infarction), hippocampus CA1 neuronal loss and myelin (Luxol Fast Blue) staining in several fiber tracts were also measured. In comparison to Sham surgery, tMCAO surgery produced significant deficits in all behavioral tests except reflex/abnormal responses. Acute, short lived deficits following tMCAO were observed for forelimb foot fault and forelimb cylinder placement. Persistent, sustained deficits for the whole 10 weeks were exhibited for motor (p<0.001), sensory (p<0.001), beam balance performance (p<0.01) and hindlimb placement behavior (p<0.01). tMCAO produced much greater and prolonged cognitive deficits in APA learning (maximum on last trial of 604±83% change, p<0.05) but only a small, comparative effect on PA retention. Hemispheric loss/atrophy was measured 10 weeks after tMCAO and cross-validated by two methods (e.g., almost identical % ischemic hemispheric loss of 33.4±3.5% for H&E and of 34.2±3.5% for TTC staining). No visual dysfunction by ERG and no hippocampus neuronal loss were detected after tMCAO. Fiber tract damage measured by Luxol Fast Blue myelin staining intensity was significant (p<0.01) in the external capsule and striatum but not in corpus callosum and anterior commissure. In summary, persistent neurobehavioral deficits were validated as important endpoints for stroke restorative research in the future. Fiber myelin loss appears to contribute to these long term behavioral dysfunctions and can be important for cognitive behavioral control necessary for complex APA learning.
Highlights
Stroke is the 4th leading cause of death and a leading cause of disability in the United States
Is cognitive decline and dementia associated with increased stroke risk [1,2], but the absolute risk for dementia is dramatically increased within the first few months following a stroke [3]
The ‘‘unsuccessful Two hours middle cerebral artery occlusion (tMCAO)’’ criteria was: (1) no exhibition of contralateral limb weakness and hemiparalysis with maintained ability to hold their head in a straight position when suspended by their tail or, (2) exhibition of moribund behavior that results from brain hemorrhage due to thread placement through a blood vessel [9]
Summary
Stroke is the 4th leading cause of death and a leading cause of disability in the United States (http://www.strokeassociation.org/ STROKEORG/AboutStroke/About-Stroke_UCM_308529_Sub HomePage.jsp). The profiling of many different sensory, motor and cognitive behaviors will provide increased opportunity to better understand brain protection and restoration of function in the future. These issues can account for the inconsistent and poorly correlated degree of infarction to severity of neurological deficits seen previously [21]. The identification of persistent neurological and cognitive deficits associated with brain changes, including injury to fiber tract systems that are essential to complex cognitive performance, are expected to provide us with a framework for investigating treatment approaches that facilitate brain restoration (i.e., reorganization, synaptic plasticity and recovery of lost function) post-stroke
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