Delayed minocycline treatment reduces long-term functional deficits and histological injury in a rodent model of focal ischemia

Hewlett, Krista A.; Corbett, Dale

doi:10.1016/j.neuroscience.2006.03.071

Cited by 67 publications

(49 citation statements)

References 39 publications

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“…Recent studies have begun to evaluate the use of this model to generate permanent histopathological damage to forelimb regions of the brain as well as impairment of forelimb function on a number of established sensorimotor tests [15,17,21,24] . While several labs have employed distinct ET-1 injection protocols to produce ischemic damage to forelimb regions of the brain [15,17,21] , no surgical standard currently exists. In the current experimental series, our first objective was to evaluate a modified ET-1 microinjection protocol using tests of forelimb sensorimotor function and histological assessments of the resulting infarct.…”

Section: Discussionmentioning

confidence: 99%

“…However these methods often result in large, inconsistently placed lesions and are often associated www.chinaphar.com Livingston-thomas JM et al Acta Pharmacologica Sinica npg with a relatively high mortality rate [11] , unless accompanied by labour-intensive post-operative care [12,13] , rendering them inadequate for studying specifically localized deficits and/ or early interventions. To gain more specific control of lesion location, reproducibility, and marked deficits to forelimb function, different rat models of focal ischemic stroke have been developed [14][15][16][17][18] . Permanent methods such as devascularization [16] and photo-irradiation of blood vessels that supply the forelimb region [18] affect surface tissue only (without accompanying damage to subcortical regions) and do not allow for restoration of blood flow to the ischemic region.…”

Section: Introductionmentioning

confidence: 99%

“…Endothelin-1 reduces local blood flow to produce ischemic injury, either when injected proximal to the MCA [19] , applied topically to the cortical surface [20] , injected intracerebrally [15] , or when used as a combination of intracerebral and topical application [21] . Intracerebral injection of ET-1 permits the induction of ischemic injury to the forelimb sensorimotor cortex as well as subcortical regions [15,17,22] allows for gradual reperfusion of circulation over the course of several hours [20,22,23] , and is characterized by a low mortality rate compared to MCAo [22,24] , making this method an attractive option for studying post-ischemic rehabilitation.…”

Section: Introductionmentioning

confidence: 99%

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A novel approach to induction and rehabilitation of deficits in forelimb function in a rat model of ischemic stroke

et al. 2012

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Aim: Constraint-induced movement therapy (CIMt), which forces use of the impaired arm following unilateral stroke, promotes functional recovery in the clinic but animal models of CIMT have yielded mixed results. The aim of this study is to develop a refined endothelin-1 (ET-1) model of focal ischemic injury in rats that resulted in reproducible, well-defined lesions and reliable upper extremity impairments, and to determine if an appetitively motivated form of rehabilitation (voluntary forced use movement therapy; FuMt) would accelerate post-ischemic motor recovery. Methods: Male Sprague Dawley rats (3 months old) were given multiple intracerebral microinjections of et-1 into the sensorimotor cortex and dorsolateral striatum. Sham-operated rats received the same surgical procedure up to but not including the drill holes on the skull. Functional deficits were assessed using two tests of forelimb placing, a forelimb postural reflex test, a forelimb asymmetry test, and a horizontal ladder test. In a separate experiment et-1 stroke rats were subjected to daily rehabilitation with FuMt or with a control therapy beginning on post-surgery d 5. Performance and post-mortem analysis of lesion volume and regional BDnF expression were measured. Results: Following microinjections of ET-1 animals exhibited significant deficits in contralateral forelimb function on a variety of tests compared with the sham group. These deficits persisted for up to 20 d with no mortality and were associated with consistent lesion volumes. FUMT therapy resulted in a modest but significantly accelerated recovery in the forelimb function as compared with the control therapy, but did not affect lesion size or BDnF expression in the ipsilesional hemisphere. Conclusion: We conclude that refined ET-1 microinjection protocols and forcing use of the impaired forelimb in an appetitively motivated paradigm may prove useful in developing strategies to study post-ischemic rehabilitation and neuroplasticity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A novel approach to induction and rehabilitation of deficits in forelimb function in a rat model of ischemic stroke

et al. 2012

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“…On a longer time scale, two studies found that minocycline improved neurological functioning and behavioral recovery when given for four days after ischemic insult in MCAO rodent model and then for four weeks [45]. In the second animal study [46], minocycline did not reduce infarct size, but did decrease the number of activated microglia while preserving plasticity in the dentate gyrus.…”

Section: Treatment With Minocycline In Humansmentioning

confidence: 98%

Minocycline: A Novel Stroke Therapy

Møller¹

2015

JNSK

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“…M groups were established by BCCAO and were given the same volume saline through douche via stomach. According to the references [5,6] , MT groups, after having been established vascular dementia model, were given minocycline through douche via stomach by 50 mg/kg, per day.…”

Section: Animals and Agentsmentioning

confidence: 99%

Minocycline attenuates cognitive impairment and restrains oxidative stress in the hippocampus of rats with chronic cerebral hypoperfusion

et al. 2008

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Objective Nitric oxide (NO) was speculated to play an important role in the pathophysiology of cerebral ischemia. Minocycline, a tetracycline derivative, reduced inflammation and protected against cerebral ischemia. To study the neuroprotection mechanism of minocycline for vascular dementia, the influences of minocycline on expressions of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were observed in the brains of Wistar rats. Methods The vascular dementia rat model was established by permanent bilateral common carotid arteries occlusion (BCCAO). Wistar rats were divideded into 3 groups randomly: sham-operation group (S group), vascular dementia model group (M group), and minocycline treatment group (MT group). The behaviour was tested with Morris water maze and open-field task. Expressions of iNOS and eNOS were measured by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). The optical density value was measured by imaging analysis. Percentage of positive cells with iNOS and eNOS expression was analyzed with optical microscope. Results Minocycline attenuated cognitive impairment. Inducible NOS was significantly down-regulated in MT group, compared with that in M group (P < 0.01), while eNOS was significantly up-regulated, compared with that in M group (P < 0.01). The expressions of iNOS and eNOS in M and MT groups were higher than those in S group (P < 0.01). Conclusion Minocycline can down-regulate the expression of iNOS and up-regulate the expression of eNOS in vascular dementia, which restrains apoptosis and oxidative stress to protect neural function.

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Delayed minocycline treatment reduces long-term functional deficits and histological injury in a rodent model of focal ischemia

Cited by 67 publications

References 39 publications

A novel approach to induction and rehabilitation of deficits in forelimb function in a rat model of ischemic stroke

A novel approach to induction and rehabilitation of deficits in forelimb function in a rat model of ischemic stroke

Minocycline: A Novel Stroke Therapy

Minocycline attenuates cognitive impairment and restrains oxidative stress in the hippocampus of rats with chronic cerebral hypoperfusion

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