Age-dependence of sensorimotor and cerebral electroencephalographic asymmetry in rats subjected to unilateral cerebrovascular stroke

Abstract

BackgroundThe human population mostly affected by stroke is more than 65 years old. This study was designed to meet the recommendation that models of cerebral ischemia in aged animals are more relevant to the clinical setting than young animal models. Until now the majority of the pre-clinical studies examining age effects on stroke outcomes have used rats of old age. Considering the increasing incidence of stroke among younger than old human population, new translational approaches in animal models are needed to match the rejuvenation of stroke. A better knowledge of alterations in stroke outcomes in middle-aged rats has important preventive and management implications providing clues for future investigations on effects of various neuroprotective and neurorestorative drugs against cerebrovascular accidents that may occur before late senescence.MethodsWe evaluated the impact of transient focal ischemia, induced by intracerebral unilateral infusion of endothelin-1 (Et-1) near the middle cerebral artery of conscious rats, on volume of brain damage and asymmetry in behavioral and electroencephalographic (EEG) output measures in middle-aged (11–12 month-old) rats.ResultsWe did not find any age-dependent difference in the volume of ischemic brain damage three days after Et-1 infusion. However, age was an important determinant of neurological and EEG outcomes after stroke. Middle-aged ischemic rats had more impaired somatosensory functions of the contralateral part of the body than young ischemic rats and thus, had greater left-right reflex/sensorimotor asymmetry. Interhemispheric EEG asymmetry was more evident in middle-aged than in young ischemic rats, and this could tentatively explain the behavioral asymmetry.ConclusionsWith a multiparametric approach, we have validated the endothelin model of ischemia in middle-aged rats. The results provide clues for future studies on mechanisms underlying plasticity after brain damage and motivate investigations of novel neuroprotective strategies against cerebrovascular accidents that may occur before late senescence.

Perturbation of Brain Oscillations after Ischemic Stroke: A Potential Biomarker for Post-Stroke Function and Therapy

“…Due to the lack of consensus in the evolution of the contralateral side, an asymmetric index is often used to reflect changes of rhythms in both hemispheres over time. This asymmetry calculated by the brain symmetry index (BSI) or the global pairwise derived brain symmetry index (pdBSI) is also present in experimental studies as reported during both acute (1 h post-stroke) and chronic phases (up to 14 days post-stroke) in young and one-year-old rats, respectively [ 161 ].…”

“…Thus, ischemia has resulted in an increase of low frequency and a decrease of high frequency oscillations, or specifically a decrease of the α-to-δ ratio [ 17 , 159 ], considering the baseline distribution as 25%–45% of δ, 40% of θ, 12%–15% of α, and 3%–20% of β oscillations [ 16 , 17 ]. In particular, an increase in δ power in the ipsilateral hemisphere after transient MCA stroke was reported in both the subacute and chronic phase from 24 h to seven days or beyond [ 16 , 17 , 160 , 161 , 162 , 163 ]. Another study reported that an increase of the ipsilateral δ and θ power occurred as early as one minute following intraluminal filament occlusion of the proximal part of MCA that leads to impairment in the subcortical brain regions [ 164 ].…”

“…Diaschisis frequently occurs after focal brain ischemia [ 166 , 167 ], of which the transhemispheric diaschisis refers to changes in the contralateral hemisphere detected after unilateral stroke [ 168 ]. Some studies suggest that an increase of the δ activity in the contralateral sensorimotor cortical areas correlated with an ipsilateral increase one to seven days after MCAO in rodents [ 16 , 159 , 161 , 169 ]. On the other hand, other studies have shown that an increase in the contralateral EEG power in the somatosensory cortex accompanied a suppression of the EEG activity in the ipsilateral side 15 min after tMCAO in rats.…”

Neurophysiological status of patients in early postoperative period after simultaneous coronary artery bypass grafting and carotid endarterectomy

“…В проведенных ранее исследованиях показано, что ишемическое повреждение мозга, даже локальное, может привести к его глобальной дисфункции, что находит свое отражение в нарушениях его нейронной активности [17]. Так, нарушения сознания, вызванные острыми эпизодами гипоперфузии мозговой ткани, сопровождаются диффузным увеличением мощности τ-и δ-активности с угнетением низко-и среднечастотного компонентов α-ритма, при этом усугубление гипоксии приводит к увеличению мощности δ-ритма и снижению мощности τ-и α-ритмов [18].…”

Present Status and Future Challenges of New Therapeutic Targets in Preclinical Models of Stroke in Aged Animals with/without Comorbidities

“…Having in mind that epidemiological studies revealed that human stroke occurs more often in late middle age (50–70 years) than at older ages (more than 70 years) it comes as quite a surprise that young animals are mostly used to test new drugs for stroke. By now, however, there is a number of reports on age-related alterations in the response to stroke at transcriptional, cellular, and electrophysiological level [ 11 , 13 , 14 , 15 , 16 , 17 , 18 ]. Therefore, extrapolating results from young animals to aged humans could lead to erroneous conclusions [ 19 , 20 ].…”