scholarly journals Impaired capillary-to-arteriolar electrical signaling after traumatic brain injury

2020 ◽  
pp. 0271678X2096259
Author(s):  
Amreen Mughal ◽  
Adrian M Sackheim ◽  
Maria Sancho ◽  
Thomas A Longden ◽  
Sheila Russell ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cerebral Hemodynamics ◽  
Laser Scanning Microscopy ◽  
Functional Hyperemia ◽  
Cranial Window ◽  
Channel Function ◽  
Inward Rectifier Potassium Channels ◽  
Electrical Signaling ◽  
Kir2.1 Channel

Traumatic brain injury (TBI) acutely impairs dynamic regulation of local cerebral blood flow, but long-term (>72 h) effects on functional hyperemia are unknown. Functional hyperemia depends on capillary endothelial cell inward rectifier potassium channels (Kir2.1) responding to potassium (K+) released during neuronal activity to produce a regenerative, hyperpolarizing electrical signal that propagates from capillaries to dilate upstream penetrating arterioles. We hypothesized that TBI causes widespread disruption of electrical signaling from capillaries-to-arterioles through impairment of Kir2.1 channel function. We randomized mice to TBI or control groups and allowed them to recover for 4 to 7 days post-injury. We measured in vivo cerebral hemodynamics and arteriolar responses to local stimulation of capillaries with 10 mM K+ using multiphoton laser scanning microscopy through a cranial window under urethane and α-chloralose anesthesia. Capillary angio-architecture was not significantly affected following injury. However, K+-induced hyperemia was significantly impaired. Electrophysiology recordings in freshly isolated capillary endothelial cells revealed diminished Ba2+-sensitive Kir2.1 currents, consistent with a reduction in channel function. In pressurized cerebral arteries isolated from TBI mice, K+ failed to elicit the vasodilation seen in controls. We conclude that disruption of endothelial Kir2.1 channel function impairs capillary-to-arteriole electrical signaling, contributing to altered cerebral hemodynamics after TBI.

scholarly journals Traumatic Brain Injury Impairs Systemic Vascular Function Through Disruption of Inward-Rectifier Potassium Channels

Function ◽  
2021 ◽  
Author(s):  
Adrian M Sackheim ◽  
Nuria Villalba ◽  
Maria Sancho ◽  
Osama F Harraz ◽  
Adrian D Bonev ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Potassium Channels ◽  
Signaling Pathways ◽  
Inward Rectifier ◽  
Pla2 Activity ◽  
Functional Responses ◽  
Channel Function ◽  
Inward Rectifier Potassium Channels ◽  
Kir2.1 Channel

Abstract Trauma can lead to widespread vascular dysfunction, but the underlying mechanisms remain largely unknown. Inward-rectifier potassium channels (Kir2.1) play a critical role in the dynamic regulation of regional perfusion and blood flow. Kir2.1 channel activity requires phosphatidylinositol 4,5-bisphosphate (PIP2), a membrane phospholipid that is degraded by phospholipase A2 (PLA2) in conditions of oxidative stress or inflammation. We hypothesized that PLA2–induced depletion of PIP2 after trauma impairs Kir2.1 channel function. A fluid percussion injury model of traumatic brain injury (TBI) in rats was used to study mesenteric resistance arteries 24 hours after injury. The functional responses of intact arteries were assessed using pressure myography. We analyzed circulating PLA2, hydrogen peroxide (H2O2), and metabolites to identify alterations in signaling pathways associated with PIP2 in TBI. Electrophysiology analysis of freshly-isolated endothelial and smooth muscle cells revealed a significant reduction of Ba2+-sensitive Kir2.1 currents after TBI. Additionally, dilations to elevated extracellular potassium and BaCl2- or ML 133-induced constrictions in pressurized arteries were significantly decreased following TBI, consistent with an impairment of Kir2.1 channel function. The addition of a PIP2 analog to the patch pipette successfully rescued endothelial Kir2.1 currents after TBI. Both H2O2 and PLA2 activity were increased after injury. Metabolomics analysis demonstrated altered lipid metabolism signaling pathways, including increased arachidonic acid, and fatty acid mobilization after TBI. Our findings support a model in which increased H2O2-induced PLA2 activity after trauma hydrolyzes endothelial PIP2, resulting in impaired Kir2.1 channel function.

scholarly journals Pathologically Entangled: Brain trauma-evoked ROS imbalance disrupts Kir channel function in distant peripheral vessels

Function ◽  
2021 ◽  
Author(s):  
Nick Weir ◽  
Thomas A Longden
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Potassium Channels ◽  
Vascular Function ◽  
Inward Rectifier ◽  
Brain Trauma ◽  
Channel Function ◽  
Inward Rectifier Potassium Channels ◽  
Kir Channel

Abstract A Perspective on "Traumatic Brain Injury Impairs Systemic Vascular Function Through Disruption of Inward-Rectifier Potassium Channels"

scholarly journals Traumatic Brain Injury Impairs Systemic Vascular Function Through Altered Lipid Metabolism and Disruption of Inward-Rectifier Potassium (Kir2.1) Channels

2021 ◽  
Author(s):  
Adrian M. Sackheim ◽  
Nuria Villalba ◽  
Maria Sancho ◽  
Osama F. Harraz ◽  
Adrian D. Bonev ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Smooth Muscle ◽  
Lipid Metabolism ◽  
Brain Injury ◽  
Smooth Muscle Cells ◽  
Inward Rectifier ◽  
Channel Function ◽  
Altered Lipid Metabolism ◽  
Altered Lipid ◽  
Kir2.1 Channel

AbstractBACKGROUND AND PURPOSETrauma can lead to widespread vascular endothelial dysfunction, but the underlying mechanisms remain largely unknown. Strong inward-rectifier potassium channels (Kir2.1) play a critical role in the dynamic regulation of regional perfusion and blood flow. Kir2.1 channel activity is modulated by phosphatidylinositol 4,5-bisphosphate (PIP2), a minor membrane phospholipid that is degraded by phospholipase A2 (PLA2) in conditions of oxidative stress or severe inflammation. We hypothesized that PLA2–induced depletion of PIP2 impairs Kir2.1 channel function.METHODSA fluid percussion injury model of traumatic brain injury (TBI) in rats was used to study mesenteric resistance arteries 24 hours after injury. Patch-clamp electrophysiology in freshly isolated endothelial and smooth muscle cells was performed to monitor Kir2.1 conductance, and the functional responses of intact arteries were assessed using pressure myography. We analyzed circulating PLA2, hydrogen peroxide (H2O2), and metabolites to identify alterations in signaling pathways associated with PIP2 in TBI.RESULTSElectrophysiology analysis of endothelial and smooth muscle cells revealed a significant reduction of Ba2+-sensitive Kir2.1 currents after TBI. Additionally, dilations to elevated extracellular potassium and BaCl2- or ML 133-induced constrictions in pressurized arteries were significantly decreased following TBI, consistent with an impairment of Kir2.1 channel function. The addition of a PIP2 analog to the patch pipette successfully rescued endothelial Kir2.1 currents after TBI. Both H2O2 and PLA2 activity were increased after injury. Metabolomics analysis demonstrated altered lipid metabolism signaling pathways, including increased arachidonic acid, and fatty acid mobilization after TBI.CONCLUSIONSOur findings support a model in which increased H2O2-induced PLA2 activity after trauma hydrolyzes endothelial PIP2, resulting in impaired Kir2.1 channel function.

Autologous Bone Marrow Mononuclear Cell Therapy for Severe Traumatic Brain Injury in Children

Neurosurgery ◽  
2011 ◽  
Vol 68 (3) ◽  
pp. 588-600 ◽  
Author(s):  
Charles S. Cox ◽  
James E. Baumgartner ◽  
Matthew T. Harting ◽  
Laura L. Worth ◽  
Peter A. Walker ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Bone Marrow ◽  
Renal Function ◽  
Brain Injury ◽  
Lung Injury ◽  
Mononuclear Cell ◽  
Severe Traumatic Brain Injury ◽  
Cerebral Hemodynamics ◽  
Hepatic Enzymes ◽  
Severe Tbi

Abstract BACKGROUND: Severe traumatic brain injury (TBI) in children is associated with substantial long-term morbidity and mortality. Currently, there are no successful neuroprotective/neuroreparative treatments for TBI. Numerous preclinical studies suggest that bone marrow-derived mononuclear cells (BMMNCs), their derivative cells (marrow stromal cells), or similar cells (umbilical cord blood cells) offer neuroprotection. OBJECTIVE: To determine whether autologous BMMNCs are a safe treatment for severe TBI in children. METHODS: Ten children aged 5 to 14 years with a postresuscitation Glasgow Coma Scale of 5 to 8 were treated with 6 × 106 autologous BMMNCs/kg body weight delivered intravenously within 48 hours after TBI. To determine the safety of the procedure, systemic and cerebral hemodynamics were monitored during bone marrow harvest; infusion-related toxicity was determined by pediatric logistic organ dysfunction (PELOD) scores, hepatic enzymes, Murray lung injury scores, and renal function. Conventional magnetic resonance imaging (cMRI) data were obtained at 1 and 6 months postinjury, as were neuropsychological and functional outcome measures. RESULTS: All patients survived. There were no episodes of harvest-related depression of systemic or cerebral hemodynamics. There was no detectable infusion-related toxicity as determined by PELOD score, hepatic enzymes, Murray lung injury scores, or renal function. cMRI imaging comparing gray matter, white matter, and CSF volumes showed no reduction from 1 to 6 months postinjury. Dichotomized Glasgow Outcome Score at 6 months showed 70% with good outcomes and 30% with moderate to severe disability. CONCLUSION: Bone marrow harvest and intravenous mononuclear cell infusion as treatment for severe TBI in children is logistically feasible and safe.

scholarly journals Diagnostics and treatment of traumatic brain injury in children

2009 ◽  
Vol 8 (1) ◽  
pp. 61-63
Author(s):  
D. V. Kolmakov
Keyword(s):  
Traumatic Brain Injury ◽  
Health Status ◽  
Brain Injury ◽  
Age Structure ◽  
Neurological Status ◽  
Cerebral Hemodynamics ◽  
Successive Treatment ◽  
Children's Hospital ◽  
Health Status Questionnaires ◽  
At Home

In this work, we have analyzed 2 774 case records of children after traumatic brain injury for the period of 2003 to 2007 (based on materials of the Tomsk Municipal Children’s Hospital No. 4). The age structure and causes of a traumatic brain injury have been analyzed. Most often complaints of children coming to the hospital are revealed, as well as typical changes in the cerebral hemodynamics (from the data of по данным rheoencephalography) and some parameters characterizing the neurological status of patients immediately after the injury and six months later. Based on the analysis of case records and health status questionnaires of children having traumatic brain injury up to six months later, it is shown that parents of patients in some cases do not adhere doctor’s recommendations after leaving the hospital. The therapy of traumatic brain injury in children requires successive treatment in hospital and at home and development of simple and acceptable rehabilitation schemes for children.

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