Axonal dysfunction in internal capsule is closely associated with early motor deficits after intracerebral hemorrhage in mice

Hijioka, Masanori; Anan, Junpei; Matsushita, Hideaki; Ishibashi, Hayato; Kurauchi, Yuki; Hisatsune, Akinori; Seki, Takahiro

doi:10.1016/j.neures.2015.10.006

Cited by 25 publications

(24 citation statements)

References 20 publications

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“…ICH is a complicated pathological status in the adult population [2]. Although many resources have been invested in clinical and basic research on ICH, there is still no effective drug that is currently available [18].…”

Section: Discussionmentioning

confidence: 99%

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Bone Marrow Mesenchymal Stem Cell Transplantation Increases GAP-43 Expression via ERK1/2 and PI3K/Akt Pathways in Intracerebral Hemorrhage

Chen

Cui

et al. 2017

Cell Physiol Biochem

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Background/Aims: Intracerebral hemorrhage (ICH) occurs in hypertensive patients and results in high rates of mortality and disability. This study determined whether bone marrow mesenchymal stem cell (BMSC) transplantation affects axonal regeneration and examined the underlying mechanisms after the administration of PD98059 (p-ERK1/2 inhibitor) or/ and LY294002 (PI3K inhibitor). The hypothesis that was intended to be tested was that BMSC transplantation regulates the expression of growth-associated protein-43 (GAP-43) via the ERK1/2 and PI3K/Akt signaling pathways. Methods: Seventy-five male rats (250-280 g) were subjected to intracerebral blood injection and then randomly received a vehicle, BMSCs, PD98059 or LY294002 treatment. Neurological deficits were evaluated prior to injury and at 1, 3 and 7 days post-injury. The expression of GAP-43, Akt, p-Akt, ERK1/2, and p-ERK1/2 proteins was measured by western blot analysis. Results: BMSC transplantation attenuated neurological deficits 3-7 days post-ICH. The expression of GAP-43 was increased 3 days following BMSC transplantation. However, this increase was inhibited by either PD98059 or LY294002 treatment. Treatment with both PD98059 and LY294002 was more effective than was treatment with an individual compound. Conclusion: BMSC transplantation could attenuate neurological deficits and activate axonal regeneration in this rat ICH model. The protective effects might be associated with increased GAP-43 expression by activating both the ERK1/2 and PI3K/Akt signaling pathways.J. Cui and C. Cui contributed equally to this work as co-first authors.

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Section: Discussionmentioning

confidence: 99%

“…Following treatment, most patients improve gradually during the first several months, but motor function recovery generally remains incomplete [2]. The motor deficits in a stroke result from an interruption of the motor fibers descending from the cortex to the spinal cord.…”

Section: Introductionmentioning

confidence: 99%

Bone Marrow Mesenchymal Stem Cell Transplantation Increases GAP-43 Expression via ERK1/2 and PI3K/Akt Pathways in Intracerebral Hemorrhage

Chen

Cui

et al. 2017

Cell Physiol Biochem

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“…We recently addressed the correlation between the histopathological events and neurological dysfunction of mice after ICH. 17) Fragmentation of axonal structures as determined by neurofilament-H immunoreactivity was evident from 6 h after ICH induced by collagenase injection near the internal capsule. In contrast, severe neurological dysfunction was observed already at 3 h after induction of ICH.…”

Section: Mechanisms and Potential Therapeutic Interventionsmentioning

confidence: 97%

“…Detailed molecular mechanisms of the action of thrombin remain an open question, and we demonstrated that stimulation of protease-activated receptor-1 was not sufficient for inhibition of axonal transport. 17) Injury of axonal tracts involves demyelination process as well as the destruction of axonal fibers. In a recent study, Zhuo et al 18) addressed the mechanisms of demyelination in rats that received autologous blood injection into the area adjacent to the internal capsule.…”

Section: Mechanisms and Potential Therapeutic Interventionsmentioning

confidence: 99%

Intracerebral Hemorrhage as an Axonal Tract Injury Disorder with Inflammatory Reactions

Katsuki

2017

Biological & Pharmaceutical Bulletin

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Intracerebral hemorrhage (ICH) is a neurological disorder frequently accompanied by severe dysfunction. Critical pathogenic events leading to poor prognosis should be identified for the development of novel effective therapies for ICH. Here we focus on the injury of the axonal tract, particularly of the internal capsule, with reference to its contribution to ICH pathology and potential therapeutic interventions in addition to its cellular mechanisms. Studies on human ICH patients and rodent models of ICH suggest that invasion of hematoma into the internal capsule greatly worsens the severity of post-ICH symptoms. A blood-derived protease thrombin may play an important role in the acute phase of axonal tract injury in the internal capsule that includes compromised axonal transport and fragmentation of axonal structures. Several agents such as clioquinol, melatonin and Am80 (a retinoic acid receptor agonist) have been shown to produce therapeutic effects on rodent models of ICH associated with injury of the internal capsule. In the course of examinations on the effect of Am80, we obtained evidence for the involvement of CXCL2, a neutrophil chemotactic factor, in the pathogenesis of ICH. Accordingly, we also refer to the potential roles of infiltrating neutrophils and inflammatory responses in axonal tract injury and resultant neurological dysfunction in ICH.

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“…Studies in both human patients with ICH and rat models of ICH show that the invasion of the hematoma into the internal capsule can cause axonal dysfunction, which would greatly aggravate the severity of symptoms after ICH. The blood‐derived protease thrombin may play a key role in the acute phase of axonal tract injury after ICH in the internal capsule through fragmentation of axonal structures, inducing axonal transport dysfunction .…”

Section: Repair or Recovery Mechanism And Strategymentioning

confidence: 99%

White matter repair and treatment strategy after intracerebral hemorrhage

et al. 2019

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The predilection site of intracerebral hemorrhage (ICH) is in the basal ganglia, which is rich in white matter (WM) fiber bundles, such as cerebrospinal tract in the internal capsule. ICH induced damage to this area can easily lead to severe neurological dysfunction and affects the prognosis and quality of life of patients. At present, the pathophysiological mechanisms of white matter injury (WMI) after ICH have attracted researchers' attention, but studies on the repair and recovery mechanisms and therapy strategies remain rare. In this review, we mainly summarized the WM recovery and treatment strategies after ICH by updating the WMI‐related content by reviewing the latest researches and proposing the bottleneck of the current research.

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Axonal dysfunction in internal capsule is closely associated with early motor deficits after intracerebral hemorrhage in mice

Cited by 25 publications

References 20 publications

Bone Marrow Mesenchymal Stem Cell Transplantation Increases GAP-43 Expression via ERK1/2 and PI3K/Akt Pathways in Intracerebral Hemorrhage

Bone Marrow Mesenchymal Stem Cell Transplantation Increases GAP-43 Expression via ERK1/2 and PI3K/Akt Pathways in Intracerebral Hemorrhage

Intracerebral Hemorrhage as an Axonal Tract Injury Disorder with Inflammatory Reactions

White matter repair and treatment strategy after intracerebral hemorrhage

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