Neural circuitry generating locomotor rhythm and pattern is located in the spinal cord. Most spinal cord injuries (SCIs) occur above the level of spinal locomotor neurons; therefore, these circuits are a target for improving motor function after SCI. Despite being relatively intact below the injury, locomotor circuitry undergoes substantial plasticity with the loss of descending control. Information regarding cell type-specific plasticity within locomotor circuits is limited. Shox2 interneurons (INs) have been linked to locomotor rhythm generation and patterning, making them a potential therapeutic target for the restoration of locomotion after SCI. The goal of the present study was to identify SCI-induced plasticity at the level of Shox2 INs in a complete thoracic transection model in adult male and female mice. Whole-cell patch-clamp recordings of Shox2 INs revealed minimal changes in intrinsic excitability properties after SCI. However, afferent stimulation resulted in mixed excitatory and inhibitory input to Shox2 INs in uninjured mice which became predominantly excitatory after SCI. Shox2 INs were differentially modulated by serotonin (5-HT) in a concentration-dependent manner in uninjured conditions but following SCI, 5-HT predominantly depolarized Shox2 INs. 5-HT 7 receptors mediated excitatory effects on Shox2 INs from both uninjured and SCI mice, but activation of 5-HT 2B/2C receptors enhanced excitability of Shox2 INs only after SCI. Overall, SCI alters sensory afferent input pathways to Shox2 INs and 5-HT modulation of Shox2 INs to enhance excitatory responses. Our findings provide relevant information regarding the locomotor circuitry response to SCI that could benefit strategies to improve locomotion after SCI.
Objective: Cerebral autoregulation limits the variability of cerebral blood flow (CBF) in the presence of systemic arterial blood pressure (ABP) changes. Monitoring cerebral autoregulation is important in the Neurocritical Care Unit (NCCU) to assess cerebral health. Here, our goal is to identify optimal frequency-domain near-infrared spectroscopy (FD-NIRS) parameters and apply a hemodynamic model of coherent hemodynamics spectroscopy (CHS) to assess cerebral autoregulation in healthy adult subjects and NCCU patients.Methods: In five healthy subjects and three NCCU patients, ABP oscillations at a frequency around 0.065 Hz were induced by cyclic inflation-deflation of pneumatic thigh cuffs. Transfer function analysis based on wavelet transform was performed to measure dynamic relationships between ABP and oscillations in oxy- (O), deoxy- (D), and total- (T) hemoglobin concentrations measured with different FD-NIRS methods. In healthy subjects, we also obtained the dynamic CBF-ABP relationship by using FD-NIRS measurements and the CHS model. In healthy subjects, an interval of hypercapnia was performed to induce cerebral autoregulation impairment. In NCCU patients, the optical measurements of autoregulation were linked to individual clinical diagnoses.Results: In healthy subjects, hypercapnia leads to a more negative phase difference of both O and D oscillations vs. ABP oscillations, which are consistent across different FD-NIRS methods and are highly correlated with a more negative phase difference CBF vs. ABP. In the NCCU, a less negative phase difference of D vs. ABP was observed in one patient as compared to two others, indicating a better autoregulation in that patient.Conclusions: Non-invasive optical measurements of induced phase difference between D and ABP show the strongest sensitivity to cerebral autoregulation. The results from healthy subjects also show that the CHS model, in combination with FD-NIRS, can be applied to measure the CBF-ABP dynamics for a better direct measurement of cerebral autoregulation.
Introduction Aneurysmal subarachnoid hemorrhage (aSAH) commonly presents with hydrocephalus due to obstruction of cerebrospinal fluid (CSF) passage across the ventricular system in the brain. Placement of an external ventricular device (EVD) and in some cases ventriculoperitoneal shunt (VPS) are often necessary for patients requiring prolonged CSF diversion. The study aimed at evaluating critical factors that play a role in determining the need for extended extraventricular drainage. Methods We performed a retrospective observational cohort study of two groups of patients with radiological imaging confirmed high grade aSAH (Hunt & Hess grades 3-5) who required VPS placement, shunt-dependent group, and who did not require long term CSF diversion, non-shunt-dependent group. We collected and analyzed data regarding the daily CSF output for 10 days following EVD placement, daily EVD height, intracranial pressure (ICP) and cerebral perfusion pressure (CPP), indicators of hydrocephalus, and CSF characteristics. Results The cohort, comprising of 8 patients in the shunt-dependent group and 32 patients in the non-shunt-dependent group, displayed median daily CSF output of 275.1 mL/day and 193.4 mL/day, respectively ( P = .0005). ROC curve for CSF drainage for the two groups showed an area under the curve (AUC) of 0.71 with a 95% confidence interval (CI) 0.65 to 0.77. Qualitative analysis of CSF characteristics revealed that the shunt-dependent group had more proteinaceous, darker red color, and greater proportion of red blood cells (RBCs) although not statistically significant. Conclusions Determinants of prolonged CSF drainage requirements in patients with high grade aSAH are not fully elucidated to this date and there is no standardized protocol for CSF diversion. Our study revealed potential markers that can be used in the assessment for the need for long term CSF diversion. Our limited sample size necessitates further research to establish clear correlations and cutoffs of these parameters in predicting long term CSF diversion requirements.
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