Neurovascular Interactions in the Nervous System.

Molecular cross talk between the nervous and vascular systems is necessary to maintain the correct coupling of organ structure and function. Molecular pathways shared by both systems are emerging as major players in the communication of the neuronal compartment with the endothelium. Here we review different aspects of this cross talk and how vessels influence the development and homeostasis of the nervous system. Beyond the classical role of the vasculature as a conduit to deliver oxygen and metabolites needed for the energy-demanding neuronal compartment, vessels emerge as powerful signaling systems that control and instruct a variety of cellular processes during the development of neurons and glia, such as migration, differentiation, and structural connectivity. Moreover, a broad spectrum of mild to severe vascular dysfunctions occur in various pathologies of the nervous system, suggesting that mild structural and functional changes at the neurovascular interface may underlie cognitive decline in many of these pathological conditions.

Novel FEMASK-score, a histopathologic assessment for destructive Charcot neuropathic arthropathy, reveals intraneural vasculopathy and correlates with progression and best treatment.

BACKGROUND: Charcot neuropathic arthropathy is a debilitating, rapidly destructive degenerative joint disease that occurs in diabetic, neuropathic midfoot. Clinicoradiologic assessment for Charcot neuropathic arthropathy previously relied on Eichenholtz stage. There is limited histopathologic data on this entity. We wanted to independently develop a histopathologic scoring system for Charcot neuropathic arthropathy. DESIGN: Retrieval of surgical pathology midfoot specimens from Charcot patients (2012-2019) were analyzed to evaluate joint soft tissue and bone. Considering progression from large (≥half 40× hpf) to small (

Sleep Deprivation Impairs the Human Central and Peripheral Nervous System Discrimination of Social Threat.

Facial expressions represent one of the most salient cues in our environment. They communicate the affective state and intent of an individual and, if interpreted correctly, adaptively influence the behavior of others in return. Processing of such affective stimuli is known to require reciprocal signaling between central viscerosensory brain regions and peripheral-autonomic body systems, culminating in accurate emotion discrimination. Despite emerging links between sleep and affective regulation, the impact of sleep loss on the discrimination of complex social emotions within and between the CNS and PNS remains unknown. Here, we demonstrate in humans that sleep deprivation impairs both viscerosensory brain (anterior insula, anterior cingulate cortex, amygdala) and autonomic-cardiac discrimination of threatening from affiliative facial cues. Moreover, sleep deprivation significantly degrades the normally reciprocal associations between these central and peripheral emotion-signaling systems, most prominent at the level of cardiac-amygdala coupling. In addition, REM sleep physiology across the sleep-rested night significantly predicts the next-day success of emotional discrimination within this viscerosensory network across individuals, suggesting a role for REM sleep in affective brain recalibration. Together, these findings establish that sleep deprivation compromises the faithful signaling of, and the "embodied" reciprocity between, viscerosensory brain and peripheral autonomic body processing of complex social signals. Such impairments hold ecological relevance in professional contexts in which the need for accurate interpretation of social cues is paramount yet insufficient sleep is pervasive.

Favorable effect of VEGF gene transfer on ischemic peripheral neuropathy.

Ischemic peripheral neuropathy is a frequent, irreversible complication of lower extremity vascular insufficiency. We investigated whether ischemic peripheral neuropathy could be prevented and/or reversed by gene transfer of an endothelial cell mitogen designed to promote therapeutic angiogenesis. Intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor (VEGF) simultaneously with induction of hindlimb ischemia in rabbits abrogated the substantial decrease in motor and sensory nerve parameters, and nerve function recovered promptly. When gene transfer was administered 10 days after induction of ischemia, nerve function was restored earlier and/or recovered faster than in untreated rabbits. These findings are due in part to enhanced hindlimb perfusion. In addition, however, the demonstration of functional VEGF receptor expression by Schwann cells indicates a direct effect of VEGF on neural integrity as well. These findings thus constitute a new paradigm for the treatment of ischemic peripheral neuropathy.

Neurovascular assessment in the critically ill patient.

AIM: To outline the pathophysiological processes involved in neurovascular impairment and compartment syndrome and examine common contributory factors within the development and clinical presentation of neurovascular impairment in critical care patients with musculoskeletal trauma. BACKGROUND: Thorough and systematic assessment of neurovascular status in critically ill patients with musculoskeletal trauma is crucial to detect secondary ischaemic injury and implement appropriate and timely treatment of any neurovascular deficits. METHOD: Current literature relating to neurovascular assessment and associated patient care was reviewed and utilised to outline distinct assessment components, indicators of neurovascular impairment and highlight the important issues for critical care nursing practice. RESULTS: Diminished limb perfusion secondary to vascular impairment and compartment syndrome are well documented. Complications associated with musculoskeletal trauma and surgical intervention can have wide-ranging effects on the patient's functional ability and overall outcome. It is crucial that appropriate neurovascular assessment is undertaken for patients admitted to the critical care unit following musculoskeletal trauma, crush injury, orthopaedic surgery (involving internal or external fixation of fractures) and those who may have experienced prolonged external pressure from casts or tight-fitting bandages. Several elements of neurovascular assessment are, however, more complex to undertake in the context of the unconscious or sedated critically ill patient. CONCLUSIONS: Effective practice requires that the critical care nurse has a comprehensive understanding of the aetiology, pathophysiology, physiological responses and clinical presentation associated with neurovascular impairment, secondary ischaemia and compartment syndrome. RELEVANCE TO CLINICAL PRACTICE: Undertaking an effective neurovascular assessment for patients at risk of neurovascular impairment or acute compartment syndrome (ACS) in the critical care setting can be problematic when patients are unable to communicate with the nurse. The risk of long-term functional impairment or limb loss can be significant in this group of patients, particularly following musculoskeletal trauma. This article reviews the aetiology and pathophysiology of neurovascular impairment in the critical care context and provides guidance for nurses undertaking this important element of nursing assessment with non-verbal, critically unwell patients. Informed practice in neurovascular assessment has the potential to enable early detection and timely management for these patients, which is crucial to optimise patient outcomes.

The effects of gender and test protocol on the results of head-up tilt test in patients with vasovagal syncope.

BACKGROUND: Head-up tilt testing (HUTT) is a well-established method for the diagnosis of reflex syncope. Some controversies exist whether gender and HUTT protocol influence HUTT results. AIM: To analyse the results of HUTT in patients with syncope in relation to their gender and used protocol of HUTT. METHODS: We retrospectively analysed data of 537 consecutive patients (313 women and 224 men), aged 13-79 years with history of neurally-mediated syncope referred to HUTT. The cardiogenic and neurological aetiology of syncope was excluded in all patients based on previous examination. In 375 patients standard HUTT (STD HUTT), according to the Westminster protocol, was used. In 257 patients in whom STD HUTT was negative, HUTT was continued with pharmacological provocation using isoproterenol intravenous infusion--114 patients (ISO HUTT) or sublingual nitroglycerin--143 patients (NTG HUTT). In the remaining 162 patients HUTT was performed according to the Italian protocol (ITL HUTT). The HUTT results were classified according to the VASIS scale. RESULTS: Female gender dominated, however, syncope was induced in a similar proportion of women and men (77.3 vs. 70.5%, NS). There were also no significant differences in the type of vasovagal response (VVR) to HUTT between women and men. Mixed type of VVR was the most frequent after isoproterenol provocation (ISO HUTT), whereas cardioinhibitory type of VVR was the most frequent after nitroglycerin provocation (NTG HUTT). CONCLUSIONS: There is no significant relationship between gender and the result of HUTT. The type of VVR is related to HUTT protocol--cardioinhibitory response is more frequent following nitroglycerin administration in comparison to standard protocol and HUTT with isoproterenol provocation.

[Anatomy and physiology of the peripheral nerve]. / Organisation anatomique et physiologique du nerf périphérique.

The peripheral nerve provides the pathway for motor, sensory and vegetative axons belonging to the peripheral nervous system. It transmits information between these neurons and their peripheral effectors in both directions (sensory receptors, skeletal muscles and viscera). The afferences to the periphery correspond to the nerve motor content, whereas efferences from the periphery, in charge of delivering information to the central integrators, correspond to nerve-sensitive content. This information support depends on intrinsic properties of the nerve itself. Recent advances in cellular and molecular biology have provided a better understanding of nerve physiology, which are reviewed here as an indispensable basis to the study of its pathology.

Microvascular networks in the area of the auditory peripheral nervous system.

Using transgenic fluorescent reporter mice in combination with an established tissue clearing method, we detail heretofore optically opaque regions of the spiral lamina and spiral limbus where the auditory peripheral nervous system is located and provide insight into changes in cochlear vascular density with ageing. We found a relatively dense and branched vascular network in young adults, but a less dense and thinned network in aged adults. Significant reduction in vascular density starts early at the age of 180 days in the region of the spiral limbus (SL) and continues into old age at 540 days. Loss of vascular volume in the region of spiral ganglion neurons (SGN) is delayed until the age of 540 days. In addition, we observed that two vascular accessory cells are closely associated with the microvascular system: perivascular resident macrophages and pericytes. Morphologically, perivascular resident macrophages undergo drastic changes from postnatal P7 to young adult (P30). In postnatal animals, most perivascular resident macrophages exhibit a spherical or nodular shape. In young adult mice, the majority of perivascular resident macrophages are elongated and display an orientation parallel to the vessels. In our imaging, some of the perivascular resident macrophages are caught in the act of transmigrating from the blood circulation. Pericytes also display morphological heterogeneity. In the P7 mice, pericytes are prominent on the capillary walls, relatively large and punctate, and less uniform. In contrast, pericytes in the P30 mice are relatively flat and uniform, and less densely distributed on the vascular network. With triple fluorescence labeling, we did not find obvious physical connection between the two systems, unlike neuronal-vascular coupling found in brain. However, using a fluorescent (FITC-conjugated dextran) tracer and the enzymatic tracer horseradish peroxidase (HRP), we observed robust neurovascular exchange, likely through transcytotic transport, evidenced by multiple vesicles present in the endothelial cells. Taken together, our data demonstrate the effectiveness of tissue-clearing methods as an aid in imaging the vascular architecture of the SL and SGNs in whole mounted mouse cochlear preparations. Structure is indicative of function. The finding of differences in vascular structure in postnatal and young adult mice may correspond with variation in hearing refinement after birth and indicate the status of functional activity. The decrease in capillary network density in the older animals may reflect the decreased energy demand from peripheral neural activity. The finding of active transcytotic transport from blood to neurons opens a potential therapeutic avenue for delivery of various growth factors and gene vectors into the inner ear to target SGNs.

Neurovascular assessment.

The ability to carry out a neurovascular assessment on a patient's limb is an important skill for all registered nurses. All nurses, whether working in primary or acute care environments, are exposed to patients who have sustained injury or trauma to a limb or have a cast or restrictive bandages in place. The ability to detect a compromised limb through careful observation enables prompt referral and subsequent treatment, which may otherwise result in a permanent deficit. This article discusses the importance of undertaking neurovascular observations providing a step-by-step guide for the reader.

Autonomic arousal index: an automated detection based on peripheral arterial tonometry.

Arousals from sleep are associated with increased sympathetic activation and are therefore associated with peripheral vasoconstriction. We hypothesized that digital vasoconstrictions as measured by peripheral arterial tonometery (PAT), combined with an increase in pulse rate, would accurately reflect arousals from sleep, and can provide an autonomic arousal index (AAI). Based on a previously studied group of 40 sleep apnea patients simultaneously recorded by both polysomnography (PSG) and PAT systems, an automated algorithm using the PAT signal (and pulse rate derived from it) was developed for detection of arousals from sleep. This was further validated in a separate group of 96 subjects (85 patients referred with suspected obstructive sleep apnea and 11 healthy volunteers mean age 46.2+/-14.4 years, BMI 28.5+/-5.4 kg/m2). All underwent a whole night PSG with simultaneous PAT recording. The PSG recordings were blindly manually analyzed for arousals based on American Academy of Sleep Medicine (AASM) criteria, while PAT was scored automatically. There was a significant correlation between PSG and PAT arousals (R=0.82, p<0.0001) with a good agreement across a wide range of values, with a ROC curve having an area under the curve (AUC) of 0.88. We conclude that automated analysis of the peripheral arterial tonometry signal can detect EEG arousals from sleep, in a relatively quick and reproducible fashion.

Responses of group III and IV muscle afferents to distension of the peripheral vascular bed.

This study was undertaken to test the hypothesis that group III and IV afferents with endings in skeletal muscle signal the distension of the peripheral vascular network. The responses of these slowly conducting afferents to pharmacologically induced vasodilation and to acute obstruction of the venous drainage of the hindlimbs were studied in barbiturate-anesthetized cats. Afferent impulses arising from endings in the triceps surae muscles were recorded from the L(7) and S(1) dorsal roots. Fifteen of the 48 group IV and 3 of the 19 group III afferents tested were stimulated by intra-aortic injections of papaverine (2-2.5 mg/kg). Sixty-two percent of the afferents that responded to papaverine also responded to isoproterenol (50 microg/kg). Seven of the 36 group IV and 2 of the 12 group III afferents tested were excited by acute distension of the hindlimb venous system. Four of the seven group IV afferents responding to venous distension also responded to papaverine (57 vs. 13% for the nonresponding). Finally, we observed that most of the group IV afferents that were excited by dynamic contractions of the triceps surae muscles also responded either to venous distension or to vasodilatory agents. These results are consistent with the histological findings that a large number of group IV endings have their receptive fields close to the venules and suggest that they can be stimulated by the deformation of these vascular structures when peripheral conductance increases. Moreover, such a mechanism offers the possibility of encoding both the effects of muscle contraction through intramuscular pressure changes and the distension of the venular system, thereby monitoring the activity of the veno-muscular pump.

A perfused rat brain model maintaining the connection between the central and peripheral nervous systems.

We have developed a new perfused brain model in rats. In this model, the cerebral circulation is separated from the systemic circulation, while the connections between the central and peripheral nervous systems are preserved. After bilateral common carotid, external carotid and vertebral artery ligation, bilateral common carotid arteries were cannulated to infuse rinsed human type O red blood cells mixed with modified Ringer's solution. To drain cerebral venous blood, external jugular veins were cannulated. Normal electrocortical activities were observed on electroencephalograms (EEGs) for more than 1h after the beginning of the perfusion. Somatosensory evoked potentials (SEPs) were also recorded. Direct infusion of pentylenetetrazol (PTZ) into the brain induced epileptic discharges on the EEGs and active dilation of cerebral arterioles, which was accompanied by an increase in systemic blood pressure (BP). The present model, in which we can change cerebral blood flow (CBF) and/or cerebral metabolism without directly affecting the systemic circulation, will provide a new approach to brain research.

Peripheral nerve vascular changes in spontaneously hypertensive rats.

Circulation to the brain is affected by hypertension. Hypertension-dependent cerebrovascular changes were documented primarily in brain pial arteries, whereas no information is so far available concerning changes of peripheral nerve vascularization in hypertension. This study was designed to assess the occurrence of structural changes of interfascicular and intrafascicular arteries supplying peripheral nerves (the so called vasa nervorum) in spontaneously hypertensive rats (SHR). The investigation was performed in 8-month-old SHR, by using standard microanatomical techniques associated with quantitative image analysis. In SHR a significant increase of systolic pressure values accompanied by thickening of the arterial wall, narrowing of the lumen and increase of the wall-to-lumen ratio were observed in comparison with age-matched normotensive Wistar-Kyoto rats. Hypertension-related structural changes involved primarily interfascicular arteries and to a lesser extent intrafascicular arteries. These findings indicate that similarly as documented for cerebral arteries, the vascular supply to peripheral nerves is impaired in hypertension. Structural changes of interfascicular and intrafascicular arteries of SHR could lead to ischemia of peripheral nerves. Further work is in progress to evaluate the functional relevance of hypertensive changes to peripheral nerve vasculature.

The susceptibility of rat diabetic nerve to ischemia: increased or decreased?

Diabetic nerve reveals a peculiar paradox between its physiological resistance to ischemia, in conducting impulses for longer than control nerve during ischemia, and its morphological liability to more severe pathological changes of nerve fiber when rendered ischemic. These paradoxical phenomena, however, have never been previously evaluated in the same diabetic rat. In the present study, the effect of ischemia on rat diabetic nerve was assessed both physiologically and morphologically at 2 and 16 weeks after the injection of streptozotocin. At 16 weeks the effects of a rapid normalization of blood glucose by insulin on these phenomena were also evaluated. Two weeks after the induction of diabetes, physiological resistance to ischemia was found, but not morphological vulnerability. After 16 weeks of diabetes, both physiological resistance and morphological vulnerability to ischemia were observed. At this time the administration of insulin had no effect on morphological vulnerability, but shortened the time of preservation of nerve action potentials during ischemia although it was not normalized. These findings indicate that the morphological liability of diabetic nerve to ischemia is most likely due to a combined effect of systemic complications of chronic hyperglycemia. By contrast a substantial component of resistance to ischemic conduction failure appears to be related to rapidly reversible metabolic derangement due to hyperglycemia. The study demonstrates coexistence of physiological resistance and morphological vulnerability to ischemia in rat diabetic nerve, and implies that different factors are involved in these paradoxical phenomena.

How to avoid and manage nerve injuries associated with aortic surgery: ischemic neuropathy, traction injuries, and sexual derangements.

Both open and endovascular surgery of the infrarenal aorta are attended by risks of neurologic complications. Injury to the periaortic autonomic plexi frequently results in ejaculatory and erectile dysfunction. Traction injuries to lumbosacral nerve roots can cause peripheral nerve injury, most commonly exhibited as a femoral nerve deficit. The least common but most feared neurologic complication that can occur with infrarenal aortic surgery is ischemic injury to the spinal cord, or conus medullaris. The risk of this complication is increased with emergent or complicated aortic reconstructions. The importance of internal iliac artery perfusion to the development of ischemic cord and nerve root injury has been recognized. Although some neurologic complications may be avoidable by technical modifications, there is a small and probably irreducible neurologic risk to aortic surgery that should be considered when weighing options for treatment of aortic pathology.

Ischemic peripheral neuropathy.

Ischemic neuropathy from sources other than diabetes is less common, but can be encountered in clinical practice. Diagnosis can be challenging, and many patients may be referred to the electrodiagnostic laboratory. Overlapping mononeuritis multiplex is a common presentation, but distal symmetric polyneuropathy and monomelic neuropathy patterns can be seen. Depending on the disease associated with ischemic neuropathy, a mononeuropathy or a sensory-motor, axonal-demyelinating peripheral neuropathy may be seen as well. The treatment of ischemic neuropathy varies depending on the associated disease. Prognosis can be poor in the case of amyloidosis and the primary vasculitides. The literature is limited to cross-sectional case series and rare longitudinal studies likely related to the incidence of the diseases. Further study is needed to fully define the extent of the neurologic consequences of peripheral ischemia and its significance clinically.

Mathematical modeling of hydrogen clearance blood flow measurements in peripheral nerve.

The hydrogen clearance technique of blood flow measurement often yields biexponential washout curves. In peripheral nerve, arteriovenous shunt vessels may clear hydrogen gas, causing the fast component of a biexponential curve. We simulated the washout of hydrogen from nerve tissue in the vicinity of a large shunt vessel by modeling the diffusion of hydrogen through tissue to the vessel and its removal by a network of capillaries. We then determined the fast and slow clearance rates and the relative weights or contributions of the fast and slow components and found that they are affected by all of the model parameters.

Avoiding tourniquet-induced neuropathy through cuff design.

Pneumatic tourniquets are routinely used in limb surgery to provide a bloodless operating field, but they are known to cause nerve injuries. Simulation results based on the hypothesis that axial compression of nerves is responsible for a certain class of these mechanically induced injuries are in substantial accord with clinical observations. A model of the limb and tourniquet that treats the tissue as a linearly elastic solid is presented and is used to predict the induced axial strains. The smallest axial strains are induced by a tourniquet design for which the applied pressure distribution rolls off as gradually as possible; according to the axial-strain hypothesis, such a design will markedly decrease a tourniquet's inherent potential for injury. Use of a wider cuff in and of itself will not reduce axial strain, so if the hypothesis is correct, a wider cuff would not be intrinsically safer than a regular cuff, a result that is contrary to current opinion.

[Adrenomedullin--the link between the sympathetic nervous system activation and peripheral vasodilatation in some patients with vasovagal syncope]. / Adrenomedullina-ogniwo laczace aktywacje ukladu wspólczulnego z obwodowa wazodylatacja u wybranych chorych z omdleniami wazowagalnymi.

UNLABELLED: Adrenomedullin (ADM) is a potent vasodilator playing role in regulation of central hemodynamic. The concentration of plasma ADM in healthy people increases under the influence of orthostatic stress. In patients with vasovagal syncope (VS) the changes in ADM concentration could be responsible either for syncope provocation or prevention. The aim of the study was to assess the influence of phase of the head-up tilt test (HUTT) in which the syncope occurred on the plasma concentration of ADM. MATERIAL AND METHODS: The study was performed in 25 patients (pts) (18 women and 7 men), mean age 45.0+/-16.1 years with cardiodepressive reactions during HUTT according to the Italian protocol with nitroglycerine (NTG) provocation if necessary: Syncope was caused in 23 pts due to vasovagal reaction: in 17 pts syncope occurred after NTG provocation (group 1), and in 6 pts occurred in the passive phase of tilt (group 2a), in 2 pts due to dysautonomic reactions (group 2b). The head-up tilt test was performed according to ESC guidelines. The blood for ADM concentration was drawn after 30 min supine rest (ADM 1) and immediately after syncope (ADM 2). ADM level was measured using radioimmunological method. The results. In group 1 plasma level of ADM significantly decreased after the HUTT (3.2+/-3.4 vs 1.7+/-1,4 pg/0.1 ml; p<0.05) and in group 2a increased significantly (1.3+/-0.8 vs 2.7+/-1.3 pg/0.1 ml; p<0.05) comparing to baseline values. The ADM concentration did not differ between the groups in baseline conditions and was significantly higher after the syncope in group 2a (p<0.05). Conclusions. The excessive increase of ADM concentration during the passive phase of HUTT could play the causative role in pathogenesis of VS occurring early during the HUTT. In patients with VS after NTG provocation the decrease of ADM concentration can be the result of hemodynamic changes in the presence of vasodilating drug and may be the mechanism that could prevent the syncope.