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BackgroundMigraine is a paroxysmal, disabling primary headache that affects 16 % of the adult population. In spite of decades of intense research, the origin and the pathophysiology mechanisms involved are still not fully known. Although triptans and gepants provide effective relief from acute migraine for many patients, their site of action remains unidentified. It has been suggested that during migraine attacks the leakiness of the blood-brain barrier (BBB) is altered, increasing the passage of anti-migraine drugs. This study aimed to investigate the effect of experimental inflammation, following dural application of complete Freund’s adjuvant (CFA) or inflammatory soup (IS) on brain and trigeminal microvascular passage.MethodsIn order to address this issue, we induced local inflammation in male Sprague-Dawley-rats dura mater by the addition of CFA or IS directly on the dural surface. Following 2, 24 or 48 h of inflammation we calculated permeability-surface area product (PS) for [51Cr]-EDTA in the trigeminal ganglion (TG), spinal trigeminal nucleus, cortex, periaqueductal grey and cerebellum.ResultsWe observed that [51Cr]-EDTA did not pass into the central nervous system (CNS) in a major way. However, [51Cr]-EDTA readily passed the TG by >30 times compared to the CNS. Application of CFA or IS did not show altered transfer constants.ConclusionsWith these experiments we show that dural IS/CFA triggered TG inflammation, did not increase the BBB passage, and that the TG is readily exposed to circulating molecules. The TG could provide a site of anti-migraine drug interaction with effect on the trigeminal system.Electronic supplementary materialThe online version of this article (doi:10.1186/s10194-015-0575-8) contains supplementary material, which is available to authorized users.

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Microvascular dysfunction in the brain, characterized by vasoconstriction, vascular occlusion, and disruption of the blood brain barrier, may adversely affect outcome following traumatic brain injury (TBI). Because of its vasodilating and antiaggregative properties, nitric oxide (NO) produced by nitric oxide synthase in the endothelium (eNOS) is a key regulator of vascular homeostasis. The objective of the present study was to evaluate the role of eNOS in vascular disturbances and histological outcome in the brain following TBI. Cortical blood flow ([(14)C]-iodoantipyrine technique), number of perfused capillaries (FITC-dextran technique), brain water content (wet vs. dry weight), and the transfer constant (K(i)) for [(51)Cr]-EDTA, reflecting permeability, were analyzed 3 h and 24 h after a controlled cortical impact injury (CCI) in eNOS-deficient (eNOS-KO) and wild-type (WT) mice. Cortical contusion volume and cell count in the hippocampus were evaluated 3 weeks after injury. Blood flow in the injured cortex decreased in both groups following trauma. There were no significant differences between the groups at 3 h, but blood flow was lower in eNOS-KO mice than in WT mice 24 h after trauma. Brain water content was higher in the WT mice than in eNOS-KO mice at 24 h. Number of perfused capillaries, K(i), and histological outcome were similar in both groups. We conclude that eNOS is important for maintenance of cerebral blood flow after trauma and that eNOS promotes edema formation by mechanisms other than increased permeability. The vascular effects of eNOS do not, however, influence histological outcome.

Prostacyclin is the major arachidonic acid metabolite of the vascular endothelium and is produced mainly via the cyclooxygenase-2 pathway. By acting on the prostacyclin (IP) receptor on platelets and vascular smooth muscle cells, prostacyclin exerts vasodilatory and antiaggregative/antiadhesive effects. Previous studies have shown that prostacyclin production increases after brain trauma, but the importance of prostacyclin for posttraumatic hemodynamic alterations and neuron survival has not been investigated. This study evaluated if endogenous prostacyclin plays a role in the pathophysiologic process in the brain after brain trauma. This was performed by comparing prostacyclin (IP) receptor-deficient (IP À/À ) mice and mice with functional IP receptor (IP + / + ) after a controlled cortical injury regarding contusion volume, cerebral blood flow ([ 14 C]iodoantipyrine autoradiography), number of perfused capillaries (fluorescein isothiocyanate-dextran fluorescence technique), the transfer constant (K i ) for [51 Cr]EDTA, and brain water content (wet vs dry weight) in the injured and contralateral cortex. Contusion volume was increased in IP À/À mice compared with IP + / + mice. Three hours after trauma, cortical blood flow was decreased in the injured cortex of both groups and the reduction in blood flow in the cortex of the IP À/À mice persisted from 3 to 24 h, whereas blood flow approached normal values in the IP + / + mice after 24 h. No differences could be detected between the two genotypes regarding other hemodynamic parameters. We conclude that the prostacyclin IP receptor is beneficial for neuron survival after brain trauma in mice, an effect that may be mediated by improved cortical perfusion.