Stimulation of the sphenopalatine ganglion induces reperfusion and blood-brain barrier protection in the photothrombotic stroke model.

PURPOSE: The treatment of stroke remains a challenge. Animal studies showing that electrical stimulation of the sphenopalatine ganglion (SPG) exerts beneficial effects in the treatment of stroke have led to the initiation of clinical studies. However, the detailed effects of SPG stimulation on the injured brain are not known. METHODS: The effect of acute SPG stimulation was studied by direct vascular imaging, fluorescent angiography and laser Doppler flowmetry in the sensory motor cortex of the anaesthetized rat. Focal cerebral ischemia was induced by the rose bengal (RB) photothrombosis method. In chronic experiments, SPG stimulation, starting 15 min or 24 h after photothrombosis, was given for 3 h per day on four consecutive days. Structural damage was assessed using histological and immunohistochemical methods. Cortical functions were assessed by quantitative analysis of epidural electro-corticographic (ECoG) activity continuously recorded in behaving animals. RESULTS: Stimulation induced intensity- and duration-dependent vasodilation and increased cerebral blood flow in both healthy and photothrombotic brains. In SPG-stimulated rats both blood brain-barrier (BBB) opening, pathological brain activity and lesion volume were attenuated compared to untreated stroke animals, with no apparent difference in the glial response surrounding the necrotic lesion. CONCLUSION: SPG-stimulation in rats induces vasodilation of cortical arterioles, partial reperfusion of the ischemic lesion, and normalization of brain functions with reduced BBB dysfunction and stroke volume. These findings support the potential therapeutic effect of SPG stimulation in focal cerebral ischemia even when applied 24 h after stroke onset and thus may extend the therapeutic window of currently administered stroke medications.

Dynamic in vivo imaging of cerebral blood flow and blood-brain barrier permeability.

The brain is characterized by an extremely rich blood supply, regulated by changes in blood vessel diameter and blood flow, depending on metabolic demands. The blood-brain barrier (BBB)-a functional and structural barrier separating the intravascular and neuropil compartments-characterizes the brain's vascular bed and is essential for normal brain functions. Disruptions to the regional cerebral blood supply, to blood drainage and to BBB properties have been described in most common neurological disorders, but there is a lack of quantitative methods for assessing blood flow dynamics and BBB permeability in small blood vessels under both physiological and pathological conditions. Here, we present a quantitative image analysis approach that allows the characterization of relative changes in the regional cerebral blood flow (rCBF) and BBB properties in small surface cortical vessels. In experiments conducted using the open window technique in rats, a fluorescent tracer was injected into the tail vein, and images of the small vessels at the surface of the cortex were taken using a fast CCD camera. Pixel-based image analysis included registration and characterization of the changes in fluorescent intensity, followed by cluster analysis. This analysis enabled the characterization of rCBF in small arterioles and venules and changes in BBB permeability. The method was implemented successfully under experimental conditions, including increased rCBF induced by neural stimulation, bile salt-induced BBB breakdown, and photothrombosis-mediated local ischemia. The new approach may be used to study changes in rCBF, neurovascular coupling and BBB permeability under normal and pathological brain conditions.