Altered physiology of gastrointestinal vagal afferents following neurotrauma

The adaptability of the central nervous system has been revealed in several model systems.Of particular interest to central nervous system-injured individuals is the ability for neural components to be modified for regain of function.In both types of neurotrauma,traumatic brain injury and spinal cord injury,the primary parasympathetic control to the gastrointestinal tract,the vagus nerve,remains anatomically intact.However,individuals with traumatic brain injury or spinal cord injury are highly susceptible to gastrointestinal dysfunctions.Such gastrointestinal dysfunctions attribute to higher morbidity and mortality following traumatic brain injury and spinal cord injury.While the vagal efferent output remains capable of eliciting motor responses following injury,evidence suggests impairment of the vagal afferents.Since sensory input drives motor output,this review will discuss the normal and altered anatomy and physiology of the gastrointestinal vagal afferents to better understand the contributions of vagal afferent plasticity following neurotrauma.

Direct evidence of VEGF-mediated neuroregulation and afferent explanation of blood pressure dysregulation during angiogenic therapy

Objective:Oncocardiology is increasingly hot research field/topic in the clinical management of cancer with anti-angiogenic therapy of vascular endothelial growth factor(VEGF)that may cause cardiovascular toxicity,such as hypertension via vascular dysfunction and attenuation of eNOS/NO signaling in the baroreflex afferent pathway.The aim of the current study was to evaluate the potential roles of VEGF/VEGF receptors(VEGFRs)expressed in the baroreflex afferent pathway in autonomic control of blood pressure(BP)regulation.Methods:The distribution and expression of VEGF/VEGFRs were detected in the nodose ganglia(NG)and nucleus of tractus solitary(NTS)using immunostaining and molecular approaches.The direct role of VEGF was tested by NG microinjection under physiological and hypertensive conditions.Results:Immunostaining data showed that either VEGF or VEGFR2/VEGFR3 was clearly detected in the NG and NTS of adult male rats.Microinjection of VEGF directly into the NG reduced the mean blood pressure(MBP)dose-dependently,which was less dramatic in renovascular hypertension(RVH)rats,suggesting the VEGF-mediated depressor response by direct activation of the 1st-order baroreceptor neurons in the NG under both normal and disease conditions.Notably,this reduced depressor response in RVH rats was directly caused by the downregulation of VEGFR2,which compensated the up regulation of VEGF/VEGFR3 in the NG during the development of hypertension.Conclusion:It demonstrated for the first time that the BP-lowering property of VEGF/VEGFRs signaling via the activation of baroreflex afferent function may be a common target/pathway leading to BP dysregulation in anti-angiogenic therapy.