Memantine Alleviates Brain Injury and Neurobehavioral Deficits after Experimental Subarachnoid Hemorrhage

Huang, Chih Yuan; Wang, Liang Chao; Wang, Hao‐Kuang; Pan, Chia Hsin; Cheng, You; Shan, Yan Shen; Chio, Chung-Ching; Tsai, Kuen‐Jer

doi:10.1007/s12035-014-8767-9

Cited by 31 publications

(22 citation statements)

References 49 publications

(75 reference statements)

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“…There are other reports that implicate the NMDAR in behavioral task dysfunction in SAH, but our study expands on these previous studies in important ways 14,31, 32, 33 . Huang and colleagues administered memantine, a low-affinity NMDA antagonist immediately after SAH.…”

Section: Discussionsupporting

confidence: 76%

“…Huang and colleagues administered memantine, a low-affinity NMDA antagonist immediately after SAH. In a more severe model of SAH that shows significant motor dysfunction, animals given memantine had improved motor function three days after hemorrhage 31 . More specifically, Chen and colleagues administered a specific NR2B inhibitor, Ro 25-6981, which improved vasospasm but showed no improvement in MWM performance at day 3 after SAH.…”

Section: Discussionmentioning

confidence: 97%

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Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors

Provencio

Swank

et al. 2016

Brain, Behavior, and Immunity

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Cognitive deficits after aneurysmal subarachnoid hemorrhage (SAH) are common and disabling. Patients who experience delayed deterioration associated with vasospasm are likely to have cognitive deficits, particularly problems with executive function, verbal and spatial memory. Here, we report neurophysiological and pathological mechanisms underlying behavioral deficits in a murine model of SAH. On tests of spatial memory, animals with SAH performed worse than sham animals in the first week and one month after SAH suggesting a prolonged injury. Between three and six days after experimental hemorrhage, mice demonstrated loss of late long-term potentiation (L-LTP) due to dysfunction of the NMDA receptor. Suppression of innate immune cell activation prevents delayed vasospasm after murine SAH. We therefore explored the role of neutrophil-mediated innate inflammation on memory deficits after SAH. Depletion of neutrophils three days after SAH mitigates tissue inflammation, reverses cerebral vasoconstriction in the middle cerebral artery, and rescues L-LTP dysfunction at day 6. Spatial memory deficits in both the short and long-term are improved and associated with a shift of NMDA receptor subunit composition toward a memory sparing phenotype. This work supports further investigating suppression of innate immunity after SAH as a target for preventative therapies in SAH.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 97%

Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors

Provencio

Swank

et al. 2016

Brain, Behavior, and Immunity

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“…Several studies on neuroprotection in SAH are being conducted (17). The drug memantine has been studied for this purpose, and its efficacy on neuroprotection in experimental SAH models has been demonstrated before (13). It was also found to be protective against SAH-induced vasospasm (14).…”

Section: Discussionmentioning

confidence: 99%

“…Memantine, which is a derivate of amantadine, is also a NMDA receptor antagonist, and its neuroprotective effects in SAH have been demonstrated in experimental animal studies (11)(12)(13). Memantine has also been found to have protective effects against SAH-induced vasospasms (14).…”

Section: Introductionmentioning

confidence: 99%

Can Amantadine Ameliorate Neurocognitive Functions After Subarachnoid Haemorrhage? A Preliminary Study

Akçıl

Dilmen

Vehid

et al. 2018

Turk J Anaesth Reanim

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Objective: Aneurysmal subarachnoid haemorrhage (SAH) may have devastating effects on patients. Motor and neurocognitive impairments may arise depending on the location and grade of the SAH. Although the effects of amantadine on neurocognitive function after traumatic brain injury have been widely studied to the best of our knowledge, their effects on recovery from SAH in humans have not been studied. The present study aimed to evaluate how amantadine influences improvement in neurocognitive function in patients with aneurysmal SAH over a period of six months. Methods: This preliminary study included 12 patients with aneurysmal SAH who were admitted to the neurointensive care unit of Cerrahpasa Faculty of Medicine. Patients in Group A (n=5) received the standard treatment for SAH and amantadine for 30 days after admission, and those in Group C (n=7) received only the standard treatment. Neurocognitive function was evaluated using the Coma Recovery Scale-Revised and Disability Rating Scale on the first and fifth days and at the third and sixth months after admission. The primary endpoint of the present study was to compare the effects of amantadine in combination with the standard treatment to those of the standard treatment alone on the neurocognitive function of patients with SAH for over 6 months. Results: Compared to the standard treatment alone, amantadine administration with the standard treatment during the early period of SAH may improve recovery. Conclusion: Amantadine along with the standard treatment can ameliorate neurocognitive function after SAH. Keywords: Amantadine, subarachnoid haemorrhage, neurocognitive functions Amaç: Anevrizmalara bağlı subaraknoid kanamalarda, kanamanın yeri ve derecesine göre motor ve nörokognitif fonksiyonlar değişik derecelerde etkilenebilmektedir. Travmatik beyin hasarı sonrası amantadinin nörokognitif fonksiyonlar üzerine etkisi geniş olarak çalışılmış olsa da, bildiğimiz kadarıyla insanlarda sunaraknoid kanama sonrası iyileşmeye etkisi çalışılmamıştır. Bu çalışmanın amacı, amantadinin anevrizmaya bağlı subaraknoid kanamalarda kanamadan sonraki 6 ay süresince nörokognitif fonksiyonları nasıl etkilediğini değerlendirmektir. Yöntemler: Bu ön çalışma anevrizmal sunaraknoid kanama tanısıyla Cerrahpaşa Tıp Fakültesi nöroyoğun bakım ünitesine kabul edilen 12 hastayı içermektedir. Grup A'da (n=5) standart subaraknoid kanama tedavisinin yanında 30 gün boyunca amantadin verilirken, Grup C'de sadece standart tedavi uygulandı (n=7). Nörokognitif fonksiyonlar; amantadin başlandığında, beşinci günde, üçüncü ve altıncı ayda "coma recovery scale-revisited" ve "disability rating scale" ile değerlendirildi. Bu çalışmanın primer sonlanım noktası, anevrizmaya bağlı subaraknoid kanaması olan hastalarda, standart tedaviye amantadin eklenmesinin kanama sonrası 6 ay süresince nörokognitif fonksiyonlardaki iyileşme üzerine olan etkilerini standart tedaviyle karşılaştırmaktır. Bulgular: Bu çalışma, anevrizmaya bağlı subaraknoid kanaması olan hastalarda, standart tedaviye amantadin eklendiğinde, ...

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“…Notably, the pathological phenomenon of excitotoxicity can also occur after hemorrhagic stroke, which is associated with poor outcome [92,93]. As aforementioned above, research studies have demonstrated that decreased expression or functional decline of KCC2 is implicated in excitotoxic neuronal death after acute CNS insults, such as TBI, SCI, and ischemic stroke.…”

Section: Kcc2 and Acute Cns Injurymentioning

confidence: 96%

The K+–Cl− Cotransporter KCC2 and Chloride Homeostasis: Potential Therapeutic Target in Acute Central Nervous System Injury

Che

Tang

et al. 2015

Mol Neurobiol

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The K(+)-Cl(-) cotransporter-2 (KCC2) is a well-known member of the electroneutral cation-chloride cotransporters with a restricted expression pattern to neurons. This transmembrane protein mediates the efflux of Cl(-) out of neurons and exerts a critical role in inhibitory γ-aminobutyric acidergic (GABAergic) and glycinergic neurotransmission. Moreover, KCC2 participates in the regulation of various physiological processes of neurons, including cell migration, dendritic outgrowth, spine morphology, and dendritic synaptogenesis. It is important to note that down-regulation of KCC2 is associated with the pathogenesis of multiple neurological diseases, which is of particular relevance to acute central nervous system (CNS) injury. In this review, we aim to survey the pathogenic significance of KCC2 down-regulation under the condition of acute CNS injuries. We propose that further elucidation of the molecular mechanisms regarding KCC2 down-regulation after acute CNS injuries is necessary because of potential promising avenues for prevention and treatment of acute CNS injury.

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Memantine Alleviates Brain Injury and Neurobehavioral Deficits after Experimental Subarachnoid Hemorrhage

Cited by 31 publications

References 49 publications

Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors

Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors

Can Amantadine Ameliorate Neurocognitive Functions After Subarachnoid Haemorrhage? A Preliminary Study

The K+–Cl− Cotransporter KCC2 and Chloride Homeostasis: Potential Therapeutic Target in Acute Central Nervous System Injury

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