scholarly journals Long-Term Spatial Cognitive Impairment after Middle Cerebral Artery Occlusion in Rats: No Involvement of the Hippocampus

1995 ◽  
Vol 15 (6) ◽  
pp. 1012-1021 ◽  
Author(s):  
Mitsuko Okada ◽  
Hiroshi Nakanishi ◽  
Akira Tamura ◽  
Akinori Urae ◽  
Kazunori Mine ◽  
...  

The behavioral and neurochemical changes in the chronic phase of permanent occlusion of the right middle cerebral artery (MCA) in rats were investigated. One month after MCA occlusion, 23 rats were unable to solve a radial eight-arm maze task during an entire 1-month period, whereas seven rats were able to solve this task. Three months after occlusion, 19 MCA-occluded rats failed to solve the task successfully again for at least 1 month (the cognitively impaired rats), whereas 11 MCA-occluded rats were able to solve it (the cognitively unimpaired rats). The rats that underwent behavioral testing were examined for any changes in the acetylcholine (ACh) levels in the hippocampus using HPLC with electrochemical detection or the formation of long-term potentiation (LTP) in the population spike of the hippocampal CA1 field. The immunohistochemical distribution of either the microtubule-associated protein 2 (MAP2) or glial fibrillary acidic protein (GFAP) in the hippocampus of the cognitively impaired rats was also studied. In the cognitively impaired rats, neither the suppression of the induction of LTP, nor the degradation of MAP2, nor the increase in the GFAP immunoreactivity was observed in the hippocampus. The levels of ACh in the hippocampus did not change significantly among the cognitively impaired, unimpaired, and the sham-operated rats. These results suggest that MCA occlusion is capable of producing long-term spatial cognitive disturbance in rats without any evidence of neurobiological damage in the hippocampus.

1995 ◽  
Vol 15 (3) ◽  
pp. 505-512 ◽  
Author(s):  
Mitsuko Okada ◽  
Akira Tamura ◽  
Akinori Urae ◽  
Tadayoshi Nakagomi ◽  
Takaaki Kirino ◽  
...  

Behavioral changes in the chronic phase of permanent occlusion of the right middle cerebral artery (MCA) in rats were investigated. One month after MCA occlusion, 23 rats were unable and 7 rats were able to solve a radial 8-arm maze task during a 1-month period. Three months after occlusion, 19 MCA-occluded rats failed to solve the task successfully again during at least a 1-month period (the cognitively impaired rats), and 11 MCA-occluded rats were able to solve it (the cognitively unimpaired rats). When a delay of 60 min was imposed for this task, five cognitively unimpaired rats failed to solve it. The locomotor activity of the cognitively impaired rats increased significantly 2 months after occlusion, and this increase showed good correlation with spatial cognitive deficit. However, the mean time a rat spent at each arm remained unchanged among the cognitively impaired, unimpaired, and sham-operated rats. There was no significant difference in the ratio between the cognitively impaired and unimpaired rats for disturbed motor coordination. These results suggest that MCA occlusion is capable of producing long-term spatial cognitive disturbance in rats. In addition, this spatial cognitive deficit does not seem to be primarily due to hypermotility or a disturbance in motor coordination.


Medicina ◽  
2021 ◽  
Vol 57 (5) ◽  
pp. 509
Author(s):  
Ho-Jun Yi ◽  
Dong-Hoon Lee ◽  
Bo-Young Hong ◽  
Seung-Yoon Song ◽  
Yeun-Jie Yoo ◽  
...  

Background and Objectives: Endovascular thrombectomy (EVT is an emerging gold standard treatment for acute cerebral infarction and may allow functional improvement after subacute cerebral infarction. However, the long-term functional benefits of EVT in patients with moderate to severe disability remain unclear. We investigated the effects of EVT on the activities of daily living (ADL), handicap, gait, and eating in patients with middle cerebral artery (MCA) occlusion who exhibited moderate to severe disability (score of 3–5 on the modified Rankin scale (mRS)) due to stroke, up to six months after onset. Materials and Methods: This retrospective longitudinal case–control study assessed 45 patients with MCA occlusion who exhibited moderate to severe disability (mRS score ≥ 3): 15 underwent EVT and 30 served as controls. Clinical assessments were conducted at two weeks (12–16 days), four weeks (26–30 days), and six months (180–210 days) after stroke onset. Functional assessments comprised the Korean version of the modified Barthel index (MBI), mRS, functional ambulation category (FAC), and dysphagia outcome severity scale (DOSS) to assess disability, handicap, gait, and eating. Results: The MBI, mRS, FAC, and DOSS scores all improved significantly (all p < 0.05) in the EVT group, compared to the controls. Conclusions: EVT has favorable effects on performing routine ADL, the handicap itself, walking, and eating. Therefore, EVT is recommended for patients with acute MCA occlusion, including those with severe disability at the initial assessment.


2021 ◽  
pp. neurintsurg-2021-017554.rep
Author(s):  
Giovanni Barchetti ◽  
Loris Di Clemente ◽  
Mauro Mazzetto ◽  
Mariano Zanusso ◽  
Paola Ferrarese ◽  
...  

We report the successful treatment of multiple ruptured fusiform middle cerebral artery (MCA) aneurysms in a 10-month-old girl. This previously healthy infant presented with subarachnoid haemorrhage and was found to have multiple irregular dilatations of the superior division branch of the right MCA. Cerebral angiography was performed and confirmed the presence of multiple fusiform aneurysms of the MCA. After multidisciplinary team discussion, it was decided to treat the aneurysms with endovascular approach, using a flow-diverter. Microsurgical clipping was deemed risky because of the high likelihood of parent artery occlusion and expectant management was also considered inappropriate because of the risk of re-bleeding. Dual antiplatelet therapy was started, and a flow-diverter was successfully delivered in the superior division branch of the right MCA. The post-operative course was uneventful, MRI at 12 months did not show any sign of recurrence and at 3 years of age the patient had a normal neurological examination.


Neurosurgery ◽  
1986 ◽  
Vol 18 (4) ◽  
pp. 397-401 ◽  
Author(s):  
Bruce I. Tranmer ◽  
Cordell E. Gross ◽  
Ted S. Keller ◽  
Glenn W. Kindt

Abstract Five consecutive patients with acute neurological deficits after middle cerebral artery (MCA) occlusion were given emergency treatment with colloidal volume expansion. In each case, the diagnosis was confirmed promptly by computed tomography and cerebral angiography. Aggressive volume expansion therapy was started 2 to 18 hours (mean, 11 hr) after the onset of the neurological deficit. The mean colloidal volume used was 920 ml/day for an average of 4 days. During volume expansion, the mean cardiac output increased 57% from 4.6 + 0.6 to 7.2 + 1.9 litres/min (P &lt; 0.05). The mean hematocrit decreased 19% from 46 + 3% to 37 + 4% (P &lt; 0.01). The mean arterial blood pressure remained stable, and the pulmonary artery wedge pressure was maintained at &lt; 15 mm Hg. Three patients improved dramatically with volume expansion therapy and have returned to their previous life-styles. Two patients made partial recoveries and manage at home with nursing care. The three patients who improved dramatically were young (aged &lt;34) and, when compared to the older patients, they had greater increases in cardiac output (67% vs. 19%). No major complications or deaths were attributed to the volume expansion therapy. We propose that intravascular volume expansion and its concomitant augmentation of the cardiovascular dynamics may be effective in the treatment of acute neurological deficits after acute MCA occlusion.


1996 ◽  
Vol 16 (4) ◽  
pp. 599-604 ◽  
Author(s):  
Zheng G. Zhang ◽  
David Reif ◽  
James Macdonald ◽  
Wen Xue Tang ◽  
Dietgard K. Kamp ◽  
...  

We tested the effects of administration of a selective neuronal nitric oxide synthase (nNOS) inhibitor, ARL 17477, on ischemic cell damage and regional cerebral blood flow (rCBF), in rats subjected to transient (2 h) middle cerebral artery (MCA) occlusion and 166 h of reperfusion (n = 48) and in rats without MCA occlusion (n = 25), respectively. Animals were administered ARL 17477 (i.v.): 10 mg/kg; 3 mg/kg; 1 mg/kg; N-nitro-L-arginine (L-NA) 10 mg/kg L-NA 1 mg/kg; and Vehicle. Administration of ARL 17477 1 mg/kg, 3 mg/kg and 10 mg/kg reduced ischemic infarct volume by 53 (p < 0.05), 23, and 6.5%, respectively. L-NA 1 mg/kg and 10 mg/kg increased infarct volume by 2 and 15%, respectively (p > 0.05). Administration of ARL 17477 (10 mg/kg) significantly (p < 0.05) decreased rCBF by 27 ± 5.3 and 24 ± 14.08% and cortical NOS activity by 86 ± 14.9 and 91 ± 8.9% at 10 min or 3 h, respectively, and did not alter mean arterial blood pressure (MABP). L-NA (10 mg/kg) significantly reduced rCBF by 23 ± 9.8% and NOS activity by 81 ± 7% and significantly (p < 0.05) increased MABP. Treatment with 3 mg/kg and 1 mg/kg ARL 17477 reduced rCBF by only 2.4 ± 4.5 and 0%, respectively, even when NOS activity was reduced by 63 ± 13.4 and 45 ± 15.7% at 3 h, respectively, (p < 0.05). The data demonstrate that ARL 17477 inhibits nNOS in the rat brain and causes a dose-dependent reduction in infarct volume after transient MCA occlusion.


2000 ◽  
Vol 20 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Tobias Neumann-Haefelin ◽  
Otto W. Witte

Transient middle cerebral artery (MCA) occlusion results in substantially smaller cortical infarcts than permanent MCA occlusion if reperfusion is initiated within the first few hours. Only little information is available on the long-term functional outcome of the cortical regions “salvaged” by early reperfusion. To address this issue we examined basic electrophysiologic parameters in vitro using standard extracellular recording techniques at 7 and 28 days after transient MCA occlusion (1- and 2-hour ischemia) in rats. Both neocortical areas ipsi- and contralateral to MCA occlusion were systematically mapped to delineate the extent of periinfarct and remote alterations. In the periinfarct region we found a significant reduction of field potential amplitudes up to 3 mm when measuring from the infarct border at 7 days and up to 7 mm at 28 days. Paired-pulse inhibition, an indicator of GABAergic transmission, was only moderately impaired in this region at 7 days and not significantly different from control at 28 days. Remote effects were observed both ipsi- and contralaterally. Ipsilaterally they were restricted to a region close to the midline (presumably motor cortex) and were most likely attributable to the degeneration of corticostriatal connections. The extent of the contralateral excitability changes was clearly related to the size of the neocortical infarcts with large infarcts resulting in the widespread reduction of field potential amplitudes and an impairment of paired-pulse inhibition. The results show that there is a relatively large periinfarct region with decreased overall excitability after transient MCA occlusion which is likely to have a profound effect on perilesional processes involved in functional recovery. Remote excitability changes may contribute to the functional deficit and are probably related to deafferentation.


2014 ◽  
Vol 121 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Bernardo Oliveira Ratilal ◽  
Mariana Moreira Coutinho Arroja ◽  
Joao Pedro Fidalgo Rocha ◽  
Adelaide Maria Afonso Fernandes ◽  
Andreia Pereira Barateiro ◽  
...  

Object There is an unmet clinical need to develop neuroprotective agents for neurosurgical and endovascular procedures that require transient cerebral artery occlusion. The aim in this study was to explore the effects of a single dose of recombinant human erythropoietin (rhEPO) before middle cerebral artery (MCA) occlusion in a focal cerebral ischemia/reperfusion model. Methods Twenty-eight adult male Wistar rats were subjected to right MCA occlusion via the intraluminal thread technique for 60 minutes under continuous cortical perfusion monitoring by laser Doppler flowmetry. Rats were divided into 2 groups: control and treatment. In the treated group, rhEPO (1000 IU/kg intravenously) was administered 10 minutes before the onset of the MCA ischemia. At 24-hour reperfusion, animals were examined for neurological deficits, blood samples were collected, and animals were killed. The following parameters were evaluated: brain infarct volume, ipsilateral hemispheric edema, neuron-specific enolase plasma levels, parenchyma histological features (H & E staining), Fluoro-Jade–positive neurons, p-Akt and total Akt expression by Western blot analysis, and p-Akt–positive nuclei by immunohistochemical investigation. Results Infarct volume and Fluoro-Jade staining of degenerating neurons in the infarct area did not vary between groups. The severity of neurological deficit (p < 0.001), amount of brain edema (78% reduction in treatment group, p < 0.001), and neuron-specific enolase plasma levels (p < 0.001) were reduced in the treatment group. Perivascular edema was histologically less marked in the treatment group. No variations in the expression or localization of p-Akt were seen. Conclusions Administration of rhEPO before the onset of 60-minute transient MCA ischemia protected the brain from this insult. It is unlikely that rhEPO pretreatment leads to direct neuronal antiapoptotic effects, as supported by the lack of Akt activation, and its benefits are most probably related to an indirect effect on brain edema as a consequence of blood-brain barrier preservation. Although research on EPO derivatives is increasing, rhEPO acts through distinct neuroprotective pathways and its clinical safety profile is well known. Clinically available rhEPO is a potential therapy for prevention of neuronal injury induced by transitory artery occlusion during neurovascular procedures.


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