Effect of Intranasally Delivered rh-VEGF165 on Angiogenesis Following Cerebral Hypoxia-Ischemia in the Cerebral Cortex of Newborn Piglets

Jain, Amit; Kratimenos, Panagiotis; Koutroulis, Ioannis; Jain, Amishi; Buddhavarapu, Amulya; Ara, Jahan

doi:10.3390/ijms18112356

Cited by 12 publications

(10 citation statements)

References 57 publications

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“…Some studies confirmed that the lesions continue to expand during the early stages of HIBD 22,23 , a result consistent with the results of this experiment; thus, internal structural changes of such lesions should be accurately assessed. Due to the strong homology between pig www.nature.com/scientificreports/ and human brain tissues 24 , newborn piglets were selected as the subjects of this experiment, and the HIBD model was successfully established in piglets in the previous experiment, and corresponding results were obtained 22 . Currently, kurtosis parameters are considered more sensitive than diffusion parameters for the evaluation of ischemic lesions by DKI 18,25 .…”

Section: Discussionmentioning

confidence: 99%

Diffusion kurtosis imaging and pathological comparison of early hypoxic–ischemic brain damage in newborn piglets

Xiao

Tian

et al. 2020

Sci Rep

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To investigate the application value of magnetic resonance diffusion kurtosis imaging (DKI) in hypoxic–ischemic brain damage (HIBD) in newborn piglets and to compare imaging and pathological results. Of 36 piglets investigated, 18 were in the experimental group and 18 in the control group. The HIBD model was established in newborn piglets by ligating the bilateral common carotid arteries and placing them into hypoxic chamber. All piglets underwent conventional MRI and DKI scans at 3, 6, 9, 12, 16, and 24 h postoperatively. Mean kurtosis (MK) and mean diffusivity (MD) maps were constructed. Then, the lesions were examined using light and electron microscopy and compared with DKI images. The MD value of the lesion area gradually decreased and the MK value gradually increased in the experimental group with time. The lesion areas gradually expanded with time; MK lesions were smaller than MD lesions. Light microscopy revealed neuronal swelling in the MK- and MD-matched and mismatched regions. Electron microscopy demonstrated obvious mitochondrial swelling and autophagosomes in the MK- and MD-matched region but normal mitochondrial morphology or mild swelling in the mismatched region. DKI can accurately evaluate early ischemic–hypoxic brain injury in newborn piglets.

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Section: Discussionmentioning

confidence: 99%

Diffusion kurtosis imaging and pathological comparison of early hypoxic–ischemic brain damage in newborn piglets

Xiao

Tian

et al. 2020

Sci Rep

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“…In this study, to further dissect out the specific contribution of HIF1α in neuronal cell death/survival, we used pharmacological strategies with a known HIF1α inhibitor 2-methoxyestradiol (2ME2), or a PHD inhibitor dimethyloxalylglycine (DMOG) that stabilizes HIF1α, to manipulate HIF1α levels in immature primary cortical neurons. We investigated whether acute manipulation of HIF1α expression has any impact on neuronal viability, as well as its effects on the HIF1α substrates, vascular endothelial growth factor (VEGF) and erythropoietin (Epo), both of which are proven to be beneficial in brain repair in rodent models of neonatal HI and neonatal stroke [22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

HIF1α Signaling in the Endogenous Protective Responses after Neonatal Brain Hypoxia-Ischemia

Liang¹,

Liu²,

Lu³

et al. 2018

Dev Neurosci

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Hypoxia-inducible factor 1α (HIF1α) is a key regulator of oxygen homeostasis, and its target genes mediate adaptive, protective, and pathological processes. The role of HIF1α in neuronal survival is controversial and the brain maturation stage is important in determining its function in brain ischemia or hypoxia-ischemia (HI). In this study, we used neuronspecific HIF1α knockout mice at postnatal day 9 (P9), and immature cortical neurons (days 7-8 in vitro) treated with the HIF1α inhibitor 2-methoxyestradiol (2ME2) or stabilizer dimethyloxalylglycine (DMOG), to examine the function of neuronal HIF1α in neonatal HI in vivo (Vannucci model) and in vitro (oxygen glucose deprivation, OGD). Inhibition of HIF1α with 2ME2 in primary neurons or deletion of neuronal HIF1α in P9 mice increased both necrotic and apoptotic cell death following HI, as evaluated by the protein levels of 145/150-kDa and 120-kDa spectrin breakdown products 24 h after HI. DMOG attenuated neuronal death right after OGD. Acute pharmacological manipulation of HIF1α synchronous-ly regulated the expression of its targets, vascular endothelial growth factor (VEGF) and erythropoietin (Epo), in the same manner. The in vivo findings agree with our previous data using the same HIF1α-deficient mice at an earlier age. This study confirms the role of neuronal HIF1α signaling in the endogenous protective responses following HI in the developing brain.

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“…The most well-recognized mechanisms of NBP activity are improving the microcirculation, promoting angiogenesis and increasing cerebral blood flow in the ischemic area. Ki-67 is a nuclear protein involved in cell proliferation, and has been used as a marker of vessel density [ 26 ]. We found that NBP treatment increased Ki-67 levels in the ischemic area in our pMCAO model, illustrating that NBP can improve angiogenesis in the ischemic region.…”

Section: Discussionmentioning

confidence: 99%

Dl-3-n-butylphthalide inhibits neuroinflammation by stimulating foxp3 and Ki-67 in an ischemic stroke model

Liu

et al. 2021

Aging

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Dl-3-n-butylphthalide (NBP) has been widely used to treat ischemic stroke in China. To investigate the mechanisms underlying NBP activity, we established a permanent middle cerebral artery occlusion (pMCAO) rat model and injected the rats with 4 mg/kg/d NBP for nine days. We then assessed neuroinflammation, neovascularization and nerve regeneration within the brain. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry imaging (MALDI-TOF MSI) was used to determine the phospholipid distribution, while laser ablation-inductively coupled plasma mass spectrometry imaging (LA-ICP MSI) was used to measure Foxp3, Ki-67 and pCREB levels in the brain. Immunohistochemistry was used to investigate the expression of NLR family pyrin domain containing 3 (NLRP3) and its inflammatory products, caspase-1 and interleukin-1β, in brain tissues. NBP attenuated ischemic damage and ameliorated neurological deficits in rats with pMCAO. In the ischemic brain region, NBP reduced phosphatidylethanolamine (18:0), NLRP3, caspase-1 and interleukin-1β levels, but increased levels of Foxp3, Ki-67, pCREB and several phospholipids. In molecular docking analyses, NBP bound to NLRP3, interleukin-1β, caspase-1, Foxp3, and Ki-67. These results demonstrate that NBP reduces neuroinflammation in brain tissues and promotes nerve and blood vessel regeneration, thus protecting neuromorphology and function.

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Effect of Intranasally Delivered rh-VEGF165 on Angiogenesis Following Cerebral Hypoxia-Ischemia in the Cerebral Cortex of Newborn Piglets

Cited by 12 publications

References 57 publications

Diffusion kurtosis imaging and pathological comparison of early hypoxic–ischemic brain damage in newborn piglets

Diffusion kurtosis imaging and pathological comparison of early hypoxic–ischemic brain damage in newborn piglets

HIF1α Signaling in the Endogenous Protective Responses after Neonatal Brain Hypoxia-Ischemia

Dl-3-n-butylphthalide inhibits neuroinflammation by stimulating foxp3 and Ki-67 in an ischemic stroke model

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