Effect of Interferon-β on Neuroinflammation, Brain Injury and Neurological Outcome After Experimental Subarachnoid Hemorrhage

Tiebosch, Ivo A C W; Dijkhuizen, Rick M.; Cobelens, Pieter M.; Bouts, Mark J. R. J.; Zwartbol, René; Meide, P. H. Van Der; Bergh, Walter M. van den

doi:10.1007/s12028-012-9692-2

Cited by 12 publications

(10 citation statements)

References 25 publications

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“…The delivery of adiponectin (30 kDa) into the brain parenchyma has also been hampered by the presence of the BBB. Previous studies have shown that many recombinant protein drugs can be introduced to avoid the shortcomings of gene therapy for clinical applications, including neurogenin-2 (Ngn2) and interferon [91,92]. The Ngn2 protein can be regulated in the CNS simply via the delivery of recombinant Ngn2 fusion protein [91].…”

Section: Discussion and Future Prospectsmentioning

confidence: 99%

The emerging role of adiponectin in cerebrovascular and neurodegenerative diseases

Yang

Jiang

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Section: Discussion and Future Prospectsmentioning

confidence: 99%

The emerging role of adiponectin in cerebrovascular and neurodegenerative diseases

Yang

Jiang

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…Both intra-and extravascular leukocytes will contribute to the inflammatory state of the brain and will reflect recruitment and influx of immune cells towards the site of injury. Cerebral inflammation detected at 48 hours after SAH seems to persist since Tiebosch et al (2013) showed an increased MPO expression even 7 days after SAH using the same endovascular puncture model [28]. Only a few reports about the expression of anti-inflammatory cytokines after SAH are available [25], [38]–[40].…”

Section: Discussionmentioning

confidence: 99%

Long-Term Functional Consequences and Ongoing Cerebral Inflammation after Subarachnoid Hemorrhage in the Rat

et al. 2014

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Subarachnoid hemorrhage (SAH) represents a considerable health problem with an incidence of 6–7 per 100.000 individuals per year in Western society. We investigated the long-term consequences of SAH on behavior, neuroinflammation and gray- and white-matter damage using an endovascular puncture model in Wistar rats. Rats were divided into a mild or severe SAH group based on their acute neurological score at 24 h post-SAH. The degree of hemorrhage determined in post-mortem brains at 48 h strongly correlated with the acute neurological score. Severe SAH induced increased TNF-α, IL-1β, IL-10, MCP-1, MIP2, CINC-1 mRNA expression and cortical neutrophil influx at 48 h post-insult. Neuroinflammation after SAH was very long-lasting and still present at day 21 as determined by Iba-1 staining (microglia/macrophages) and GFAP (astrocytes). Long-term neuroinflammation was strongly associated with the degree of severity of SAH. Cerebral damage to gray- and white-matter was visualized by immunohistochemistry for MAP2 and MBP at 21 days after SAH. Severe SAH induced significant gray- and white-matter damage. MAP2 loss at day 21 correlated significantly with the acute neurological score determined at 24 h post-SAH. Sensorimotor behavior, determined by the adhesive removal task and von Frey test, was affected after severe SAH at day 21. In conclusion, we are the first to show that SAH induces ongoing cortical inflammation. Moreover, SAH induces mainly cortical long-term brain damage, which is associated with long-term sensorimotor damage.

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“…Most animals were part of a drug treatment study in which animals received subcutaneous injection of either 0.022 mg/kg interferon-β (n = 16) or vehicle (n = 14) [9]. That study revealed no differences in lesion size, neurological status and mortality rate between treatment groups, and therefore, data were pooled.…”

Section: Methodsmentioning

confidence: 99%

Progression of Brain Lesions in Relation to Hyperperfusion from Subacute to Chronic Stages after Experimental Subarachnoid Hemorrhage: A Multiparametric MRI Study

et al. 2013

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Background: The pathogenesis of delayed cerebral injury after aneurysmal subarachnoid hemorrhage (SAH) is largely unresolved. In particular, the progression and interplay of tissue and perfusion changes, which can significantly affect the outcome, remain unclear. Only a few studies have assessed pathophysiological developments between subacute and chronic time points after SAH, which may be ideally studied with noninvasive methods in standardized animal models. Therefore, our objective was to characterize the pattern and correlation of brain perfusion and lesion status with serial multiparametric magnetic resonance imaging (MRI) from subacute to chronical after experimental SAH in rats. Methods: SAH was induced by endovascular puncture of the intracranial bifurcation of the right internal carotid artery in adult male Wistar rats (n = 30). Diffusion-, T2-, perfusion- and contrast-enhanced T1-weighted MRI were performed on a 4.7-tesla animal MR system to measure cytotoxic and vasogenic edema, hemodynamic parameters and blood-brain barrier permeability, respectively, at days 2 and 7 after SAH. The neurological status was repeatedly monitored with different behavioral testsbetween days -1 and 7 after SAH. Lesioned tissue - identified by edema-associated T2 prolongation - and unaffected tissue were outlined on multislice images and further characterized based on tissue and perfusion indices. Correlation analyses were performed to evaluate relationships between different MRI-based parameters and between MRI-based parameters and neurological scores. Results: Similar to clinical SAH and previous studies in this experimental SAH model, mortality up to day 2 was high (43%). In surviving animals, neurological function was significantly impaired subacutely, and tissue damage (characterized by T2 prolongation and diffusion reduction) and blood-brain barrier leakage (characterized by contrast agent extravasation) were apparent in ipsilateral cortical and subcortical tissue as well as in contralateral cortical tissue. Notably, ipsilateral cortical areas revealed increased cerebral blood flow and volume. Animals that subsequently died between days 2 and 7 after SAH had markedly elevated ipsilateral perfusion levels at day 2. After a week, neurological function had improved in surviving animals, and brain edema was partially resolved, while blood-brain barrier permeability and hyperperfusion persisted. The degree of brain damage correlated significantly with the level of perfusion elevation (r = 0.78 and 0.85 at days 2 and 7, respectively; p < 0.05). Furthermore, chronic (day 7 after SAH) blood-brain barrier permeability and vasogenic edema formation were associated with subacute (day 2 after SAH) hyperperfusion (r = 0.53 and 0.66, respectively; p < 0.05). Conclusion: Our imaging findings indicate that SAH-induced brain injury at later stages is associated with progressive changes in tissue perfusion and that chronic hyperperfusion may contribute or point to delayed cerebral damage. Furthermore, multiparametric MRI may significan...

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Effect of Interferon-β on Neuroinflammation, Brain Injury and Neurological Outcome After Experimental Subarachnoid Hemorrhage

Cited by 12 publications

References 25 publications

The emerging role of adiponectin in cerebrovascular and neurodegenerative diseases

The emerging role of adiponectin in cerebrovascular and neurodegenerative diseases

Long-Term Functional Consequences and Ongoing Cerebral Inflammation after Subarachnoid Hemorrhage in the Rat

Progression of Brain Lesions in Relation to Hyperperfusion from Subacute to Chronic Stages after Experimental Subarachnoid Hemorrhage: A Multiparametric MRI Study

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