Recovery and brain reorganization after stroke in adult and aged rats

Markus, Tiffanie; Tsai, Shih-Yen; Bollnow, Melanie R.; Farrer, Robert G.; O’Brien, Timothy E.; Kindler-Baumann, Diana; Rausch, Martin; Rudin, Markus; Wiessner, Christoph; Mir, Anis K.; Schwab, Martin E.; Kartje, Gwendolyn L.

doi:10.1002/ana.20676

Cited by 120 publications

(118 citation statements)

References 22 publications

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“…18 Such a reduction of Nogo-A expression could play a role in lengthening the period over which effective poststroke neuronal remodeling may occur in the rat cerebral cortex, resulting in an increase in functional recovery from poststroke deficits, as observed previously. 3,5,24,38 Normal and Poststroke Nogo-A Expression by PV ؉ Interneurons…”

Section: Discussion Neuronal Nogo-a Expression In Normal Rat Cortexmentioning

confidence: 99%

Nogo-A Expression After Focal Ischemic Stroke in the Adult Rat

Cheatwood

Emerick

Schwab

et al. 2008

Stroke

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106

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Background and Purpose-The Nogo-A protein is an important inhibitor of axonal remodeling after central nervous system injuries, including ischemic stroke. Interfering with the function of Nogo-A via infusion of a therapeutic anti-Nogo-A antibody after stroke increases neuronal remodeling and enhances functional recovery in rats. In this study, we describe the regional distribution of cortical neurons expressing Nogo-A in normal rats and following middle cerebral artery occlusion (MCAO). Methods-Normal and post-MCAO neuronal Nogo-A expression were described via immunohistochemical analyses. All brains were processed for Nogo-A and parvalbumin expression. The level of Nogo-A expression was scored for each cortical area or white matter structure of interest. The number and fluorescent intensity of layer V neurons in contralesional sensorimotor forelimb cortex were also assessed at each time point. Results-Nogo-A expression was observed in both cortical pyramidal neurons and parvalbumin-positive interneurons.Neuronal expression of Nogo-A changed over time in ipsilesional and contralesional cortical areas after MCAO, becoming globally elevated at 28 days after stroke. Nogo-A expression was not observed to fluctuate greatly in the white matter after stroke, with the exception of a transient increase in Nogo-A expression in the external capsule near the stroke lesion. Conclusions-Neuronal Nogo-A expression is significantly increased at 28 days post-MCAO in all examined brain regions. Because of their robust expression of Nogo-A after stroke lesion, both excitatory and inhibitory neurons represent potential targets for anti-Nogo-A therapies in the poststroke cerebral cortex.

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Section: Discussion Neuronal Nogo-a Expression In Normal Rat Cortexmentioning

confidence: 99%

Nogo-A Expression After Focal Ischemic Stroke in the Adult Rat

Cheatwood

Emerick

Schwab

et al. 2008

Stroke

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106

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“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Umeda

Takahashi

Isa

et al. 2010

Journal of Neurophysiology

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Neonatally hemidecorticated rats show fairly normal reaching and grasping behaviors of the forelimb contralateral to the lesion at the adult stage. Previous experiments using an anterograde tracer showed that the corticospinal fibers originating from the sensorimotor cortex of the intact side projected aberrant collaterals to the spinal gray matter on the ipsilateral side. The present study used electrophysiological methods to investigate whether the aberrant projections of the corticospinal tract mediated the pyramidal excitation to the ipsilateral forelimb motoneurons and, if so, which pathways mediate the effect in the hemidecorticated rats. Electrical stimulation to the intact medullary pyramid elicited bilateral negative field potentials in the dorsal horn of the spinal cord. In intracellular recordings of forelimb motoneurons, oligosynaptic pyramidal excitation was detected on both sides of the spinal cord in the hemidecorticated rats, whereas pyramidal excitation of motoneurons on the side ipsilateral to the stimulation was much smaller in normal rats. By lesioning the dorsal funiculus at the upper cervical level, we clarified that the excitation was transmitted to the ipsilateral motoneurons by at least two pathways: one via the corticospinal tract and spinal interneurons and the other via the cortico-reticulo-spinal pathways. These results suggested that in the neonatally hemidecorticated rats, the forelimb movements on the side contralateral to the lesion were modulated by motor commands through the indirect ipsilateral descending pathways from the sensorimotor cortex of the intact side either via the spinal interneurons or reticulospinal neurons.

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“…Therefore, studies on behavioral recuperation after stroke in aged animals are necessary and welcome. Various experimental settings have been use to assess the recovery of sensorimotor functions, spontaneous activity and memory after stroke in aged rats [13,15,16,23] . Overall, the results indicate that aged rats have the capacity to recover behaviorally after cortical infarcts, albeit to a lesser extent than the young counterparts [12,13,15,20,23] .…”

Section: Aged Animals Recover More Slowly and Less Completely Than Yomentioning

confidence: 99%

“…Although it is well known that aging is a risk factor for stroke [6][7][8][9] , the majority of experimental studies of stroke have been performed on young animals, and therefore may not fully replicate the effects of ischemia on neural tissue in aged subjects [10][11][12][13] . In this light, the aged post-acute animal model is clinically most relevant to stroke rehabilitation and cellular studies, a recommendation made by the STAIR committee [14] and more recently by the Stroke Progress Review Group [15] .…”

mentioning

confidence: 99%

Cellular and Molecular Events Underlying the Dysregulated Response of the Aged Brain to Stroke: A Mini-Review

Petcu

Sfredel

Platt³

et al. 2007

Gerontology

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cells were rapidly incorporated into the glial scar, but these neuroepithelial-like cells did not make a significant contribution to neurogenesis in the infarcted cortex in young or aged animals. The response of plasticity-associated proteins like MAP1B, was delayed in aged rats. Tissue recovery was further delayed by an age-related increase in the amount of the neurotoxic C-terminal fragment of the ␤ -amyloid precursor protein (A-␤ ) at 2 weeks poststroke. Conclusion: The available evidence indicates that the aged brain has the capability to mount a cytoproliferative response to injury, but the timing of the cellular and genetic response to cerebral insult is dysregulated in aged animals, thereby further compromising functional recovery. Elucidating the molecular basis for this phenomenon in the aging brain could yield novel approaches to neurorestoration in the elderly.

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Recovery and brain reorganization after stroke in adult and aged rats

Cited by 120 publications

References 22 publications

Nogo-A Expression After Focal Ischemic Stroke in the Adult Rat

Nogo-A Expression After Focal Ischemic Stroke in the Adult Rat

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

Cellular and Molecular Events Underlying the Dysregulated Response of the Aged Brain to Stroke: A Mini-Review

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