Chronic ibuprofen treatment does not affect the secondary pathology in the thalamus or improve behavioral outcome in middle cerebral artery occlusion rats

Lipsanen, Anu; Hiltunen, Mikko; Jolkkonen, Jukka

doi:10.1016/j.pbb.2011.04.019

Cited by 18 publications

(14 citation statements)

References 42 publications

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“…MCAO rats showed a large corticostriatal lesion followed by secondary damage/pathology in the thalamus [23], which may contribute to late impairment. Indeed, delayed worsening in several gait parameters was observed at postoperative day 42.…”

Section: Discussionmentioning

confidence: 99%

Gait Impairment in a Rat Model of Focal Cerebral Ischemia

Parkkinen

Ortega

Kuptsova

et al. 2013

Stroke Research and Treatment

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The availability of proper tests for gait evaluation following cerebral ischemia in rats has been limited. The automated, quantitative CatWalk system, which was initially designed to measure gait in models of spinal cord injury, neuropathic pain, and peripheral nerve injury, is said to be a useful tool for the study of motor impairment in stroke animals. Here we report our experiences of using CatWalk XT with rats subjected to transient middle cerebral artery occlusion (MCAO), during their six-week followup. Large corticostriatal infarct was confirmed by MRI in all MCAO rats, which was associated with severe sensorimotor impairment. In contrast, the gait impairment was at most mild, which is consistent with seemingly normal locomotion of MCAO rats. Many of the gait parameters were affected by body weight, walking speed, and motivation despite the use of a goal box. In addition, MCAO rats showed bilateral compensation, which was developed to stabilize proper locomotion. All of these interferences may confound the data interpretation. Taken together, the translational applicability of CatWalk XT in evaluating motor impairment and treatment efficacy remains to be limited at least in rats with severe corticostriatal infarct and loss of body weight.

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Section: Discussionmentioning

confidence: 99%

Gait Impairment in a Rat Model of Focal Cerebral Ischemia

Parkkinen

Ortega

Kuptsova

et al. 2013

Stroke Research and Treatment

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“…We have previously shown that APP and Aβ or their fragments accumulate in dense, plaque-like deposits in the thalamus of rats subjected to transient middle cerebral artery occlusion (MCAO) [15]. This coincides with delayed retrograde degeneration of thalamocortical connections and a robust inflammatory reaction [9]. Recently we also demonstrated that APP processing and the expression of Aβ-degrading enzymes are subsequently altered due to MCAO in the ipsilateral thalamus [16].…”

Section: Introductionmentioning

confidence: 92%

“…Several studies have shown that AD and ischemic brain injury lead to altered amyloid precursor protein (APP) processing, β-amyloid (Aβ) accumulation [4]–[7], and increased neuroinflammation [8], [9] in cortical areas adjacent to the injury. More importantly, transgenic AD mice, such as APP SWE and wtAPP751, show increased vulnerability to ischemic damage [10], [11].…”

Section: Introductionmentioning

confidence: 99%

Non-Selective Calcium Channel Blocker Bepridil Decreases Secondary Pathology in Mice after Photothrombotic Cortical Lesion

et al. 2013

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Experimental studies have identified a complex link between neurodegeneration, β-amyloid (Aβ) and calcium homeostasis. Here we asked whether early phase β-amyloid pathology in transgenic hAPPSL mice exaggerates the ischemic lesion and remote secondary pathology in the thalamus, and whether a non-selective calcium channel blocker reduces these pathologies. Transgenic hAPPSL (n = 33) and non-transgenic (n = 30) male mice (4–5 months) were subjected to unilateral cortical photothrombosis and treated with the non-selective calcium channel blocker bepridil (50 mg/kg, p.o., once a day) or vehicle for 28 days, starting administration 2 days after the operation. Animals were then perfused for histological analysis of infarct size, Aβ and calcium accumulation in the thalamus. Cortical photothrombosis resulted in a small infarct, which was associated with atypical Aβ and calcium accumulation in the ipsilateral thalamus. Transgenic mice had significantly smaller infarct volumes than non-transgenic littermates (P<0.05) and ischemia-induced rodent Aβ accumulation in the thalamus was lower in transgenic mice compared to non-transgenic mice (P<0.01). Bepridil decreased calcium load in the thalamus (P<0.01). The present data suggest less pronounced primary and secondary pathology in hAPPSL transgenic mice after ischemic cortical injury. Bepridil particularly decreased calcium pathology in the thalamus following ischemia.

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“…Neuroinflammation has been implicated in SND, as demonstrated by an increase in resident inflammatory cells, such as microglia [ 174 , 177 , 178 , 179 ] and astrocytes [ 180 , 181 , 182 , 183 ], as well as infiltrating peripheral inflammatory cells, such as T cells [ 184 ] ( Table 1 ). Most interestingly, various studies have reported a spike in inflammation preceding neuronal damage in the thalamus, hippocampus and the substantia nigra (SN), a critical part of the basal ganglia ( Figure 1 ) [ 51 , 177 , 182 , 185 ].…”

Section: Neuroinflammation In Sndmentioning

confidence: 99%

Neuroinflammation as a Key Driver of Secondary Neurodegeneration Following Stroke?

Stuckey

Ong

Collins-Praino

et al. 2021

IJMS

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Ischaemic stroke involves the rapid onset of focal neurological dysfunction, most commonly due to an arterial blockage in a specific region of the brain. Stroke is a leading cause of death and common cause of disability, with over 17 million people worldwide suffering from a stroke each year. It is now well-documented that neuroinflammation and immune mediators play a key role in acute and long-term neuronal tissue damage and healing, not only in the infarct core but also in distal regions. Importantly, in these distal regions, termed sites of secondary neurodegeneration (SND), spikes in neuroinflammation may be seen sometime after the initial stroke onset, but prior to the presence of the neuronal tissue damage within these regions. However, it is key to acknowledge that, despite the mounting information describing neuroinflammation following ischaemic stroke, the exact mechanisms whereby inflammatory cells and their mediators drive stroke-induced neuroinflammation are still not fully understood. As a result, current anti-inflammatory treatments have failed to show efficacy in clinical trials. In this review we discuss the complexities of post-stroke neuroinflammation, specifically how it affects neuronal tissue and post-stroke outcome acutely, chronically, and in sites of SND. We then discuss current and previously assessed anti-inflammatory therapies, with a particular focus on how failed anti-inflammatories may be repurposed to target SND-associated neuroinflammation.

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Chronic ibuprofen treatment does not affect the secondary pathology in the thalamus or improve behavioral outcome in middle cerebral artery occlusion rats

Cited by 18 publications

References 42 publications

Gait Impairment in a Rat Model of Focal Cerebral Ischemia

Gait Impairment in a Rat Model of Focal Cerebral Ischemia

Non-Selective Calcium Channel Blocker Bepridil Decreases Secondary Pathology in Mice after Photothrombotic Cortical Lesion

Neuroinflammation as a Key Driver of Secondary Neurodegeneration Following Stroke?

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