RESUMEN
Autoregulatory responses of perforating arteries play a key role in the maintenance of microcirculation of the deep brain regions. The aim of this study was to test our hypothesis that autoregulatory vasodilatation of perforating arteries is more effective than that of cortical arteries. We performed cerebral microangiography in adult Wistar rats using monochromatic synchrotron radiation at SPring-8 and for the first time radiographically visualized perforating arteries and cortical arteries simultaneously in a single view. In response to hypotension induced by arterial bleeding, both arteries showed significant vasodilatation. Steady-state responses of increments in caliber to stepwise hypotension revealed that perforating arteries exhibited significant vasodilatation at blood pressure below 80-99 mm Hg. Cortical arteries, on the other hand, showed a gradual and smaller vasodilatation beginning at 60-79 mm Hg. For the lowest blood pressure range at 40-59 mm Hg, the smallest arteries with a diameter of 20-40 microm showed maximal dilation in both groups, but perforating arteries showed significantly larger dilatation (185.0% of baseline diameter) than cortical arteries (152.7%; P=0.003). Our results indicate that vasodilatation of perforating arteries is more sensitive and pronounced in response to systemic hypotension than that of pial arteries, which explains how cerebral microcirculation is maintained efficiently in the deep brain regions.
Asunto(s)
Angiografía Cerebral/métodos , Arterias Cerebrales/diagnóstico por imagen , Arterias Cerebrales/fisiopatología , Hipotensión/diagnóstico por imagen , Hipotensión/fisiopatología , Animales , Arteriolas/diagnóstico por imagen , Arteriolas/fisiopatología , Presión Sanguínea , Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/diagnóstico por imagen , Circulación Cerebrovascular , Homeostasis , Masculino , Piamadre/irrigación sanguínea , Piamadre/diagnóstico por imagen , Ratas , Ratas Wistar , VasodilataciónRESUMEN
Microangiography with spatial resolution in the micrometer range was carried out to depict vascular responses of the cerebral artery and arterioles in rats and mice using a real-time imaging system and a third generation synchrotron radiation source at SPring-8. An X-ray direct-conversion type detector with 6 microm spatial resolution was developed for real-time biomedical imaging. The X-ray image is converted directly into an electrical signal in the photoconductive layer without image blurring. In synchrotron radiation radiography, a long source-to-object distance and a small source spot can produce high-resolution images. Microangiographic images were obtained without image blurring and were stored in a digital frame memory system with a 1024 x 1024-pixel, 10-bit format. In imaging experiments, vasoconstriction and vasodilatation of small cerebral arteries were visualized in response to hypercapnia, hemorrhagic hypotension, and vasoactive agents after iodine contrast agent injection into the carotid artery.
Asunto(s)
Angiografía/métodos , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Sincrotrones , Animales , Arterias Carótidas/diagnóstico por imagen , Circulación Cerebrovascular/efectos de los fármacos , Compresión de Datos/métodos , Hemorragia/diagnóstico por imagen , Hipercapnia/diagnóstico por imagen , Hipotensión/diagnóstico por imagen , Ratones , Ratas , Vasoconstricción/efectos de los fármacos , Vasoconstrictores/farmacologíaRESUMEN
Diabetes mellitus increases the risk of cerebrovascular disease, the effects of hypercapnia on CBF (cerebral blood flow) and cerebrovascular reactivity during diabetes are still inconsistent. Here, we have established a new microangiographic technique using synchrotron radiation (SPring-8, Japan), which enabled us to visualize rat cerebral vessels with high spatial resolution in real time. The goal of the study presented here was to identify the effects of chronic hyperglycemia on hypercapnia-induced vascular responses (endothelium-dependent vasodilatation) and nitric oxide (NO) donor- induced vascular responses (endothelium-independent) of perforating arteries and of the deeply located large cerebral arteries. We found a significant vasodilatation of rat perforating arteries after hypercapnia with a maximum diameter of approximately 140% of baseline in normal Wistar rats. Chronic hyperglycemia impaired vasodilatation of perforating arteries in genetically diabetic GK rats. SNP (sodium nitroprusside) caused a similar vasodilatation of perforating vessels in normal and chronic hyperglycemia, indicating that endothelium-dependent vasodilatation of perforating arteries may be specifically impaired in chronic hyperglycemia. Possible impairment of endothelium-dependent vasodilatation in perforating vessels during chronic hyperglycemia may cause decreased vascular reserve capacity of perforating artery, resulting in the increased ischemic insults and cerebrovascular diseases in diabetes.
Asunto(s)
Arterias Cerebrales/fisiopatología , Hipercapnia/fisiopatología , Hiperglucemia/fisiopatología , Animales , Encéfalo/irrigación sanguínea , Dióxido de Carbono/administración & dosificación , Angiopatías Diabéticas/fisiopatología , Endotelio Vascular/fisiopatología , Masculino , Donantes de Óxido Nítrico/farmacología , Nitroprusiato/farmacología , Ratas , Ratas Endogámicas WKY , Vasodilatación/efectos de los fármacosRESUMEN
D-fructose-1,6-bisphosphate (FBP) is an endogenous intermediate of glycolytic pathway which has potent neuroprotective effect against various neurotoxic insults. This study examined whether FBP could antagonize the neurotoxicity induced by amyloid beta-peptide (Abeta) in rat hippocampal organotypic slice cultures, and the possible mechanism was also explored. Treatment with FBP (concentration ranges from 1.7 mM to 10 mM) significantly decreased the cell death in hippocampal slices in the presence of Abeta at 24h, 48 h and 72 h, and this neuroprotective effect of FBP against Abeta was not in a dose-dependent manner, FBP 3.5 mM has better neuroprotective effect than that of other FBP concentration groups. Treatment with FBP slightly but significantly increases the ATP levels in hippocampal slices in the presence of Abeta. However, the increment of ATP levels was similar among various FBP concentration groups. Neuroprotective effect of FBP 3.5 mM against Abeta induced neurotoxicity in hippocampal slices was attenuated by addition of phospholipase C (PLC) inhibitor, U73122, mitogen activated extracellular signal protein kinase (MEK) inhibitor, U0126, or extracellular signal activated protein kinase (ERK) inhibitor, PD98059 at 24 h, 48 h and 72 h. However, co-treatment with these three kinds of inhibitors did not change the FBP's effect on ATP levels. Our results suggested FBP has neuroprotective effect against Abeta induced neurotoxicity in hippocampal slice cultures, and FBP plays role not only as an alternative energy source, but also a modulator of PLC and MEK/ERK pathways to regulate the cellular response and survival.