scholarly journals CO2 Has no Therapeutic Effect on Early Micro Vasospasm after Experimental Subarachnoid Hemorrhage

2014 ◽  
Vol 34 (8) ◽  
pp. e1-e6 ◽  
Author(s):  
Benjamin Friedrich ◽  
Radoslaw Michalik ◽  
Anna Oniszczuk ◽  
Khalid Abubaker ◽  
Ewa Kozniewska ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Therapeutic Potential ◽  
Cerebral Arteries ◽  
Early Brain Injury ◽  
Sprague Dawley ◽  
Therapeutic Approaches ◽  
Sprague Dawley Rats ◽  
Experimental Subarachnoid Hemorrhage ◽  
Cerebral Arterioles ◽  
Cerebral Vasodilator

In addition to delayed vasospasm also early brain injury, which occurs during the first few days after subarachnoid hemorrhage (SAH) when large cerebral arteries are still fully functional, plays an important role for the outcome after SAH. In the current study, we investigated the hypothesis that carbon dioxide (CO2), a strong cerebral vasodilator, has a therapeutic potential against early posthemorrhagic microvasospasm. C57BL/6 mice ( n = 36) and Sprague-Dawley rats ( n = 23) were subjected to sham surgery or SAH by filament perforation. The pial microcirculation in the mice was visualized 3 and 24 hours after SAH using intravital fluorescence microscopy. Partial pressure of CO2 (PaCO2) was modulated by hyper- or hypoventilation or by inhalation of 10% CO2. In rats, CO2-mediated changes in cerebral blood flow (CBF) were measured at the same time points using laser Doppler fluxmetry. Increased PaCO2 caused vasodilatation in sham-operated animals. Following SAH, however, cerebral arterioles were nonreactive to CO2. This lack of microvascular CO2 reactivity was accompanied by a complete loss of CO2-induced hyperemia. Our data show that CO2 is not able to dilate spastic microvessels and to increase CBF early after SAH. Future therapeutic approaches will therefore need to address mechanisms beyond CO2.

scholarly journals Minocycline attenuates experimental subarachnoid hemorrhage in rats

2019 ◽  
Vol 14 (1) ◽  
pp. 595-602
Author(s):  
Jingbo Li ◽  
Shuda Chen ◽  
Jing Fan ◽  
Gao Zhang ◽  
Reng Ren
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Hemorrhage ◽  
Early Brain Injury ◽  
Neurological Function ◽  
Neurological Deficits ◽  
Sprague Dawley ◽  
Minocycline Treatment ◽  
Sprague Dawley Rats ◽  
Therapeutic Mechanism ◽  
Experimental Subarachnoid Hemorrhage

AbstractBackgroudThe aim of this study was to evaluate the therapeutic effect of minocycline on treating experimental subarachnoid hemorrhage (SAH) in rats and to explore its possible molecular mechanism.MethodsSAH was induced in male Sprague-Dawley rats by endovascular perforation. The rats were treated with minocycline (25 mg/kg or 50 mg/kg) or saline at 2 hand 12 h post SAH. Neurological function, cerebral hemorrhage, and edema were scored at 48 h post SAH. Cell death and P2X4 receptor (P2X4R) expression were observed in the prefrontal cortex (PFC).ResultsTreatment with a highdose of minocycline significantly improved the neurological function score, and attenuated cerebral hemorrhage and edema. Low-dose minocycline could reduce hemorrhage, but the effect on neurological deficits and brain edema was not obvious. Minocycline treatment could alleviate neuronal apoptosis in the PFC, which was related to reduced expression of inflammatory cytokines. Immunofluorescence showed that P2X4R on microglia was activated after SAH. Minocycline treatment inhibited P2X4R activation and further suppressed the phosphorylation of downstream p38 MAPK.ConclusionsMinocycline plays a neuroprotective role by attenuating early brain injury after experimental SAH. The therapeutic mechanism of minocycline may be mediated by the inhibition of P2X4R on microglia.

scholarly journals Vitamin D attenuates cerebral artery remodeling through VDR/AMPK/eNOS dimer phosphorylation pathway after subarachnoid hemorrhage in rats

2017 ◽  
Vol 39 (2) ◽  
pp. 272-284 ◽  
Author(s):  
Budbazar Enkhjargal ◽  
Jay Malaguit ◽  
Wing M Ho ◽  
Wu Jiang ◽  
Weifeng Wan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Artery ◽  
Therapeutic Strategy ◽  
Cerebral Arteries ◽  
Sprague Dawley ◽  
Enos Expression ◽  
Sprague Dawley Rats ◽  
Artery Remodeling

The role of vitamin D3 (VitD3) in the upregulation of osteopontin (OPN) and eNOS in the endothelium of cerebral arteries after subarachnoid hemorrhage (SAH) is investigated. The endovascular perforation SAH model in Sprague-Dawley rats ( n = 103) was used. The VitD3 pretreatment (30 ng/kg) increased endogenous OPN and eNOS expression in cerebral arteries compared with naïve rats ( n = 5 per group). Neurobehavioral scores were significantly improved in Pre-SAH+VitD3 group compared with the SAH group. The effects of VitD3 were attenuated by intracerebroventricular (i.c.v) injections of siRNA for the vitamin D receptor (VDR) and OPN in Pre-SAH+VitD3+VDR siRNA and Pre-SAH+VitD3+OPN siRNA rats, respectively ( n = 5 per group). The significant increase of VDR, OPN and decrease of C44 splicing in the cerebral arteries of Pre-SAH+VitD3 rats lead to an increase in basilar artery lumen. The increase in VDR expression led to an upregulation and phosphorylation of AMPK and eNOS, especially dimer form, in endothelium of cerebral artery. The results provide that VitD3 pretreatment attenuates cerebral artery remodeling and vasospasm through the upregulation of OPN and phosphorylation of AMPK (p-AMPK) and eNOS (p-eNOS) at Ser1177-Dimer in the cerebral arteries. Vitamin D may be a useful new preventive and therapeutic strategy against cerebral artery remodeling in stroke patients.

Signaling Pathways for Early Brain Injury after Subarachnoid Hemorrhage

2004 ◽  
Vol 24 (8) ◽  
pp. 916-925 ◽  
Author(s):  
Gen Kusaka ◽  
Mami Ishikawa ◽  
Anil Nanda ◽  
D. Neil Granger ◽  
John H. Zhang
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
Signaling Pathways ◽  
Brain Edema ◽  
Kinase Inhibitor ◽  
Cerebral Arteries ◽  
Early Brain Injury ◽  
Sprague Dawley ◽  
Bbb Permeability

Few studies have examined the signaling pathways that contribute to early brain injury after subarachnoid hemorrhage (SAH). Using a rat SAH model, the authors explored the role of vascular endothelial growth factor (VEGF) and mitogen-activation protein kinase (MAPK) in early brain injury. Male Sprague-Dawley rats (n = 172) weighing 300 to 350 g were used for the experimental SAH model, which was induced by puncturing the bifurcation of the left anterior cerebral and middle cerebral arteries. The blood–brain barrier (BBB), brain edema, intracranial pressure, and mortality were evaluated at 24 hours after SAH. The phosphorylation of VEGF and different MAPK subgroups (ERK1/2, p38, and JNK) were examined in both the cortex and the major cerebral arteries. Experimental SAH increased intracranial pressure, BBB permeability, and brain edema and produced high mortality. SAH induced phosphorylation of VEGF and MAPKs in the cerebral arteries and, to a lesser degree, in the cortex. PP1, an Src-family kinase inhibitor, reduced BBB permeability, brain edema, and mortality and decreased the phosphorylation of VEGF and MAPKs. The authors conclude that VEGF contributes to early brain injury after SAH by enhancing the activation of the MAPK pathways, and that the inhibition of these pathways might offer new treatment strategies for SAH.

scholarly journals Levosimendan as a therapeutic strategy to prevent neuroinflammation after aneurysmal subarachnoid hemorrhage?

2021 ◽  
pp. neurintsurg-2021-017504
Author(s):  
Stefan Wanderer ◽  
Lukas Andereggen ◽  
Jan Mrosek ◽  
Sepide Kashefiolasl ◽  
Gerrit Alexander Schubert ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Severe Heart Failure ◽  
Prostaglandin F2alpha ◽  
Sprague Dawley ◽  
Delayed Cerebral Vasospasm ◽  
Sprague Dawley Rats ◽  
Solvent Control ◽  
Anti Inflammatory

BackgroundPoor patient outcomes after aneurysmal subarachnoid hemorrhage (SAH) occur due to a multifactorial process, mainly involving cerebral inflammation (CI), delayed cerebral vasospasm (DCVS), and delayed cerebral ischemia, followed by neurodegeneration. CI is mainly triggered by enhanced synthesis of serotonin (5-HT), prostaglandin F2alpha (PGF2a), and cytokines such as interleukins. Levosimendan (LV), a calcium-channel sensitizer, has already displayed anti-inflammatory effects in patients with severe heart failure. Therefore, we wanted to elucidate its potential anti-inflammatory role on the cerebral vasculature after SAH.MethodsExperimental SAH was induced by using an experimental double-hemorrhage model. Sprague Dawley rats were harvested on day 3 and day 5 after the ictus. The basilar artery was used for isometric investigations of the muscular media tone. Vessel segments were either preincubated with LV or without, with precontraction performed with 5-HT or PGF2a followed by application of acetylcholine (ACh) or LV.ResultsAfter preincubation with LV 10−4 M and 5-HT precontraction, ACh triggered a strong vasorelaxation in sham segments (LV 10−4 M, Emax 65%; LV 10−5 M, Emax 48%; no LV, Emax 53%). Interestingly, SAH D3 (LV 10−4, Emax 76%) and D5 (LV 10−4, Emax 79%) segments showed greater vasorelaxation compared with sham. An LV series after PGF2a precontraction showed significantly enhanced relaxation in the sham (P=0.004) and SAH groups (P=0.0008) compared with solvent control vessels.ConclusionsLV application after SAH seems to beneficially influence DCVS by antagonizing 5-HT- and PGF2a-triggered vasoconstriction. Considering this spasmolytic effect, LV might have a role in the treatment of SAH, additionally in selected patients suffering takotsubo cardiomyopathy.

scholarly journals Expression signatures of long non-coding RNAs in early brain injury following experimental subarachnoid hemorrhage

2015 ◽  
Vol 12 (1) ◽  
pp. 967-973 ◽  
Author(s):  
BINGJIE ZHENG ◽  
HUAILEI LIU ◽  
RUKE WANG ◽  
SHANCAI XU ◽  
YAOHUA LIU ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Early Brain Injury ◽  
Experimental Subarachnoid Hemorrhage ◽  
Non Coding Rnas

scholarly journals TGFβ-activated Kinase 1 (TAK1) Inhibition by 5Z-7-Oxozeaenol Attenuates Early Brain Injury after Experimental Subarachnoid Hemorrhage

2015 ◽  
Vol 290 (32) ◽  
pp. 19900-19909 ◽  
Author(s):  
Dingding Zhang ◽  
Huiying Yan ◽  
Hua Li ◽  
Shuangying Hao ◽  
Zong Zhuang ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Early Brain Injury ◽  
Experimental Subarachnoid Hemorrhage
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