Treatment of intracerebral hemorrhage: What should we do now?

Wang, David Z.; Talkad, Arun

doi:10.1007/s11910-009-0003-z

Cited by 10 publications

(4 citation statements)

References 48 publications

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“…We included all controlled studies that compared stem cell therapy to vehicle or no-treatment in vivo models of ICH, in which the outcome was measured with neurobehavioral score or tissue loss or brain water content. To prevent bias, the inclusion criteria were prespecified as follows: (1) Experimental ICH was induced and the therapeutic effect of stem cells was assessed, no restriction on animal species, as well as gender, age, weight, and sample size; (2) Controlled studies with control group (receiving vehicle, saline, or no treatment) and experimental group (receiving xenogenic or allogeneic or syngeneic cell therapy), and there was no restriction on the dosage of stem cell, animal model of ICH, and time of initial treatment;…”

Section: Inclusion and Exclusion Criteriamentioning

confidence: 99%

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Efficacy of stem cell therapy in animal models of intracerebral hemorrhage: an updated meta-analysis

Qin

Zeng

et al. 2022

Stem Cell Res Ther

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Background Multiple studies have reported that stem cell therapy has beneficial effects in animal models of intracerebral hemorrhage (ICH). However, this finding remains inconclusive. This study was performed to systematically determine the effect size of stem cell therapy in ICH animal models by pooling and analyzing data from newly published studies. Methods A literature search identified studies of stem cells in animal models of ICH. We searched mainstream databases from inception to November, 2021. And pooled effect size of stem cells was determined for diversified neurobehavioral scales and structural endpoints using random effects models. Results The median quality score of 62 included studies was 5.32. Our results revealed an overall positive effect of stem cell therapy. More specifically, the SMD was − 2.27 for mNSS, − 2.14 for rotarod test, − 2.06 for MLPT, − 1.33 for cylinder test, − 1.95 for corner turn test, − 1.42 for tissue loss, and − 1.86 for brain water content. For mNSS, classifying comparisons by quality score showed significant differences in estimates of effect size (p = 0.013), and high-quality comparisons showed a better outcome (SMD = − 2.57) compared with low-quality comparisons (SMD = − 1.59). Besides, different delivery routes also showed a significant difference in the estimates of effect size for mNSS (p = 0.002), and the intraperitoneal route showed the best outcome (SMD = − 4.63). For tissue loss, the autologous blood-induced ICH model showed a better outcome (SMD = − 1.84) compared with the collagenase-induced ICH model (SMD = − 0.94, p = 0.035). Additionally, stem cell therapy initiated within 8 h post-ICH showed the greatest efficacy on tissue loss reduction, followed by initiated with 24 h post-ICH. Finally, stem cells with different sources and types showed similar beneficial effects for mNSS as well as tissue loss. Conclusions Our results suggested that stem cell therapy had remarkable benefits on ICH animals on both the functional and structural outcomes in animal models of ICH, with very large effect size. These findings support the utility of further studies to translate stem cells in the treatment of ICH in humans. Moreover, the results should be interpreted in the light of the limitations in experimental design and the methodological quality of the studies included in the meta-analysis.

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Section: Inclusion and Exclusion Criteriamentioning

confidence: 99%

“…Nontraumatic intracerebral hemorrhage (ICH) is highly associated with mortality and morbidity, with a substantially worse prognosis than ischemic stroke [ 1 , 2 ]. The mortality rate of acute ICH is approximately 40% in the first three weeks, and those who survived often suffer from different degrees of neurological deficit [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of stem cell therapy in animal models of intracerebral hemorrhage: an updated meta-analysis

Qin

Zeng

et al. 2022

Stem Cell Res Ther

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“…Intracerebral hemorrhage (ICH) is the non-traumatic hemorrhage caused by rupture of blood vessels in brain parenchyma, which is one of most fatal subtypes of stroke (Wang and Talked, 2009). It has attracted board attention because of its high morbidity and mortality worldwide (Adeoye and Broderick, 2010;Luo, 2010).…”

Section: Introductionmentioning

confidence: 99%

Systematic Review and Meta-Analysis of Randomized Controlled Trials of Liangxue Tongyu Formula on Patients With Acute Intracerebral Hemorrhage

et al. 2020

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Background: As a traditional Chinese medicine (TCM) prescription for acute stroke, Liangxue Tongyu formula (LXTYF) was widely used as auxiliary treatment measure in some clinical practice. This study aimed to evaluate the clinical efficacy and safety of LXTYF combined western conventional medicine (WCM) with WCM only for acute intracerebral hemorrhage (ICH). Methods:We systematically searched PubMed, Embase, Cochrane Library, CMB (Chinese biomedicine database), CNKI (China National Knowledge Infrastructure), WanFang, and VIP until August 2019 to confirm relevant randomized controlled trials (RCTs) compared the combination of LXTYF and WCM with WCM alone for the treatment of acute ICH. Two investigators independently assessed the risk of bias, and extracted and analyzed the data from the identified studies using RevMan 5.3.0 software following Cochrane's standard and PRISMA guidelines. The herbal compositions of LXTYF were also assessed.Results: 15 RCTs were identified, totally recruiting 1648 patients with acute intracerebral hemorrhage. Compared with the WCM alone, the combination therapy of LXTYF with WCM could improve the clinical effective rate (RR, 1.21; 95% CI, 1.15-1.25, P < 0.05) and ADL score (MD, 18.09; 95% CI, 12.11-24.07; P < 0.05), and reduce syndrome scores of the TCM (MD, −4.11; 95% CI, −4.69 to −3.53; P < 0.05) and the Glasgow outcome score (GOS) (MD=0.43, 95%CI: 0.06 to 0.79, P=0.02) Moreover, there was no sufficient evidence to indicate the adverse effects would increase compared with WCM alone.Conclusion: Based on current evidence, we concluded that the combined therapy had some benefits in treating acute intracerebral hemorrhage. However, considering the potential biases and limitations of our study, additional large, high-quality RCTs are required in the future to confirm or refute the effects of LFTYF combined with WCM in acute stroke.

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“…Spontaneous intracerebral hemorrhage (ICH) is one of the most lethal types of stroke [ 1 ] with the highest mortality and morbidity [ 2 ]. Conventional therapies for ICH consist of hematoma removal, edema attenuation and intracranial pressure reduction.…”

Section: Introductionmentioning

confidence: 99%

Buyang huanwu decoction promotes angiogenesis via vascular endothelial growth factor receptor-2 activation through the PI3K/Akt pathway in a mouse model of intracerebral hemorrhage

Cui

Yang

Zhou

et al. 2015

BMC Complement Altern Med

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BackgroundIntracerebral hemorrhage (ICH) is a fatal subtype of stroke that lacks effective treatments. Angiogenesis following ICH is an important response mediating brain recovery and repair. Phosphorylation of vascular endothelial growth factor receptor 2 (pVEGFR2) via PI3K/Akt signaling plays a key role in mediating cellular processes involved in repair, such as mitogenesis, angiogenesis, and vascular permeability. This study aimed to investigate the potential effects of Buyang Huanwu Decoction (BYHWD), a traditional Chinese medicine formula, on angiogenesis by VEGFR2 activation through the phosphatidylinositol 3 kinase (PI3K)/Akt signaling pathway in a mouse model of ICH.MethodsAdult male Kunming mice (n = 50) were randomly assigned into sham and ICH-operated groups and treated with one of the followings SU5416 (VEGFR2 inhibitor), BYHWT and BYHWT + SU5416. ICH was induced in mice by injecting collagenase (type VII) into the right globus pallidus of the mouse brain. BYHWD (4.36 g/kg) was administrated in mice by intragastric infusion. Neurological function was evaluated in mice by a modified Neurological Severity Scores (mNSS) as well as corner turn and foot-fault tests. Angiogenesis was examined by intraperitoneal injection of 5-bromodeoxyuridine (BrdU) in mice to quantify new brain vessel growth. SU5416 treatment and assessment of VEGFR2 phosphorylation as well as alterations in PI3K/Akt signaling were performed to determine whether the effect of BYHWD on angiogenesis was partly mediated by phosphorylation of VEGFR2 via the PI3K/Akt signaling pathway.ResultsWe show that BYHWD treated mice exhibited (i) significantly better recovery from neurological dysfunction, (ii) increased BrdU+ nuclei in vWF+ dilated brain vessels and (iii) higher VEGFR2 phosphorylation immunoreactivity in brain microvessels (P <0.05), (iv) higher expression of PI3K and pAkt at the protein level (P <0.05) when compared to untreated ICH mice. These beneficial effects were reversed by SU5416 (P <0.05).ConclusionsBYHWD promoted neurological recovery and angiogenesis after ICH in mice by enhancing VEGFR2 phosphorylation through the PI3K/Akt signaling pathway.

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Treatment of intracerebral hemorrhage: What should we do now?

Cited by 10 publications

References 48 publications

Efficacy of stem cell therapy in animal models of intracerebral hemorrhage: an updated meta-analysis

Efficacy of stem cell therapy in animal models of intracerebral hemorrhage: an updated meta-analysis

Systematic Review and Meta-Analysis of Randomized Controlled Trials of Liangxue Tongyu Formula on Patients With Acute Intracerebral Hemorrhage

Buyang huanwu decoction promotes angiogenesis via vascular endothelial growth factor receptor-2 activation through the PI3K/Akt pathway in a mouse model of intracerebral hemorrhage

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