Role of Circulatory disturbances in the development of post-ischemic brain edema

Masaoka, Hiroyuki; Klatzo, Igor; Tomida, Shuichi; Vass, Karl; Wagner, H. G.; Nowak, Thaddeus S.

doi:10.1007/bf03160354

Cited by 10 publications

(2 citation statements)

References 16 publications

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“…62 Others have also identified it in vascular/perivascular brain cells. 63 We detected an increased expression of GPR81 during brain development from P7 to P11 in WT mice that normalized at P15 and coincided with vascular development as inferred to by delay in vascular development in absence of GPR81, and conversely its acceleration upon lactate stimulation. This suggestion is consistent with a GPR81-dependent regulation of angiogenesis by modulating the expression of several growth factors as shown here and elsewhere.…”

Section: Discussionmentioning

confidence: 69%

“…61,62 Hence restoration of appropriate perfusion by inducing angiogenesis during stroke can ameliorate ischemia and improve outcome as previously suggested. 63 A similar paradigm had been proposed for the succinate receptor GPR91 in HIE; GPR91 promoted brain revascularization via a prostaglandin-mediated secretion of proangiogenic factors including VEGF, ANG-1, ANG-2 and IL-6. 39 TSP-1 is also an important endogenous inhibitor of angiogenesis.…”

Section: Discussionmentioning

confidence: 79%

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Neuronal GPR81 regulates developmental brain angiogenesis and promotes brain recovery after a hypoxic ischemic insult

Chaudhari

Madaan

Rivera

et al. 2022

J Cereb Blood Flow Metab

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Perinatal hypoxic/ischemic (HI) brain injury is a major clinical problem with devastating neurodevelopmental outcomes in neonates. During HI brain injury, dysregulated factor production contributes to microvascular impairment. Glycolysis-derived lactate accumulated during ischemia has been proposed to protect against ischemic injury, but its mechanism of action is poorly understood. Herein, we hypothesize that lactate via its G-protein coupled receptor (GPR81) controls postnatal brain angiogenesis and plays a protective role after HI injury. We show that GPR81 is predominantly expressed in neurons of the cerebral cortex and hippocampus. GPR81-null mice displayed a delay in cerebral microvascular development linked to reduced levels of various major angiogenic factors and augmented expression of anti-angiogenic Thrombospondin-1 (TSP-1) in comparison to their WT littermates. Coherently, lactate stimulation induced an increase in growth factors (VEGF, Ang1 and 2, PDGF) and reduced TSP-1 expression in neurons, which contributed to accelerating angiogenesis. HI injury in GPR81-null animals curtailed vascular density and consequently increased infarct size compared to changes seen in WT mice; conversely intracerebroventricular lactate injection increased vascular density and diminished infarct size in WT but not in GPR81-null mice. Collectively, we show that lactate acting via GPR81 participates in developmental brain angiogenesis, and attenuates HI injury by restoring compromised microvasculature.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 79%

Neuronal GPR81 regulates developmental brain angiogenesis and promotes brain recovery after a hypoxic ischemic insult

Chaudhari

Madaan

Rivera

et al. 2022

J Cereb Blood Flow Metab

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Time- and pressure-dependent changes in blood-brain barrier permeability after temporary middle cerebral artery occlusion in rats

et al. 1991

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After 180 min of temporary middle cerebral artery occlusion in rats, the affect of phenylephrine-induced hypertension on blood-brain barrier permeability was assessed. One of the following blood-pressure regimens was maintained during either a 30- or 120-min period of reperfusion: (a) 30/Norm, 30 min of normotensive reperfusion was allowed; (b) 30/HTN, mean arterial blood pressure was increased by 35 mm Hg during 30 min of reperfusion; (c) 120/Norm, 120 min of normotensive reperfusion was allowed; or (d) 120/HTN, mean arterial blood pressure was increased by 35 mm Hg during 120 min of reperfusion. Evans blue (30 mg/kg) was given, and brains were analyzed for Evans blue by spectrophotometry. Evans blue (microgram/g brain tissue, mean +/- SD) was greater (P less than 0.05) in both hypertensive groups versus their time matched normotensive groups (30/HTN: 80 +/- 16 versus 18 +/- 6 in the 30/Norm group; 120/HTN: 17 +/- 6 versus 8 +/- 3 in the 120/Norm group). In addition, Evans blue was greater (P less than 0.05) in both 30-min groups versus their pressure matched 120-min groups (30/Norm: 18 +/- 6 versus 8 +/- 3 in the 120/Norm group; 30/HTN: 80 +/- 16 versus 17 +/- 6 in the 120/HTN group). The data are consistent with previous studies which have demonstrated an opening of the blood-brain barrier at the onset of reperfusion. In addition, the data support a hypothesis that changes in blood-brain barrier permeability are more sensitive to hypertension in the early period of reperfusion.

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Bioenergetics of cerebral ischemia: A cellular perspective

2008

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Role of Circulatory disturbances in the development of post-ischemic brain edema

Cited by 10 publications

References 16 publications

Neuronal GPR81 regulates developmental brain angiogenesis and promotes brain recovery after a hypoxic ischemic insult

Neuronal GPR81 regulates developmental brain angiogenesis and promotes brain recovery after a hypoxic ischemic insult

Time- and pressure-dependent changes in blood-brain barrier permeability after temporary middle cerebral artery occlusion in rats

Bioenergetics of cerebral ischemia: A cellular perspective

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