Intracranial dynamics biomarkers at traumatic cerebral vasospasm.

Introduction: Patients who suffer severe traumatic brain injury (sTBI) and cerebral vasospasm (CVS) frequently have posttraumatic cerebral ischemia (PCI). The research question: was to study changes in cerebral microcirculatory bed parameters in sTBI patients with CVS and with or without PCI. Material and methods: A total of 136 severe TBI patients were recruited in the study. All patients underwent perfusion computed tomography, intracranial pressure monitoring, and transcranial Doppler. The levels of cerebrovascular resistance (CVR), cerebral arterial compliance (CAC), cerebrovascular time constant (CTC), and critical closing pressure (CCP) were measured using the neuromonitoring complex. Statistical analysis was performed using parametric and nonparametric methods and factor analysis. The patients were dichotomized into PCI-positive (n = 114) and PCI-negative (n = 22) groups. Data are presented as mean values (standard deviations). Results: CVR was significantly increased, whereas CAC, CTC, and CCP were significantly decreased in sTBI patients with CVS and PCI development (p < 0.05). Factor analyses revealed that all studied microcirculatory bed parameters were significantly associated with the development of PCI (p < 0.05). Discussion and conclusion: The changes in all studied microcirculatory bed parameters in TBI patients with CVS were significantly associated with PCI development, which enables us to regard them as the biomarkers of CVS and PCI development. The causes of the described microcirculatory bed parameters changes might include complex (cytotoxic and vasogenic) brain edema development, regional microvascular spasm, and dysfunction of pericytes. A further prospective study is warranted.

Placement of a Catheter into the Transverse Sinus in Monitoring Intracranial Lesions: A Technical Note.

High intracranial pressure (ICP) can be induced by stroke, brain trauma, and brain tumor, and lead to cerebral injury. Monitoring the blood flow of a damaged brain is important for detecting intracranial lesions. Blood sampling is a better way to monitor changes in brain oxygen and blood flow than computed tomography perfusion and magnetic resonance imaging. This article describes how to take blood samples from the transverse sinus in a high ICP rat model. Also, it compares the blood samples from the transverse sinus and femoral artery/vein through blood gas analysis and neuronal cell staining. The findings may be of significance to the monitoring of the oxygen and blood flow of intracranial lesions.

Arteriovenous cerebral blood flow correlation in moderate-to-severe traumatic brain injury: CT perfusion study.

Introduction: The relationship between arterial and venous blood flow in moderate-to-severe traumatic brain injury (TBI) is poorly understood. The research question: was to compare differences in perfusion computed tomography (PCT)-derived arterial and venous cerebral blood flow (CBF) in moderate-to-severe TBI as an indication of changes in cerebral venous outflow patterns referenced to arterial inflow. Material and methods: Moderate-to-severe TBI patients (women 53; men 74) underwent PCT and were stratified into 3 groups: I (moderate TBI), II (diffuse severe TBI without surgery), and III (severe TBI after the surgery). Arterial and venous CBF were measured by PCT in both the internal carotid arteries (CBFica) and the confluence of upper sagittal, transverse, and straight sinuses (CBFcs). Results: In group I, CBFica on the left and right sides were significantly correlated with each other (p < 0.0001) and with CBFcs (p = 0.048). In group II, CBFica on the left and right sides were also correlated (P < 0.0000001) but not with CBFcs. Intracranial pressure reactivity (PRx) and CBFcs were correlated (p = 0.00014). In group III, CBFica on the side of the removed hematoma was not significantly different from the opposite CBFica (P = 0.680) and was not correlated with CBFcs. Discussion and conclusion: The increasing severity of TBI is accompanied by a rising uncoupling between the arterial and venous CBF in the supratentorial vessels suggesting a shifting of cerebral venous outflow.

Dynamics of Intracranial Pressure and Cerebrovascular Reactivity During Intrahospital Transportation of Traumatic Brain Injury Patients in Coma.

BACKGROUND: Intrahospital transportation (IHT) of patients with traumatic brain injury (TBI) is common and may have adverse consequences, incurring inherent risks. The data on the frequency and severity of clinical complications linked with IHT are contradictory, and there is no agreement on whether it is safe or potentially challenging for neurocritical care unit patients. Continuous intracranial pressure (ICP) monitoring is essential in neurointensive care. The role of ICP monitoring and management of cerebral autoregulation impairments in IHT of patients with severe TBI is underinvestigated. The purpose of this nonrandomized retrospective single-center study was to assess the dynamics of ICP and an improved pressure reactivity index (iPRx) as a measure of autoregulation during IHT. METHODS: Seventy-seven men and fourteen women with severe TBI admitted in 2012-2022 with a mean age of 33.2 ± 5.2 years were studied. ICP and arterial pressure were invasively monitored, and cerebral perfusion pressure and iPRx were calculated from the measured parameters. All patients were subjected to dynamic helical computed tomography angiography using a 64-slice scanner Philips Ingenuity computed tomography scan 1-2 days after TBI. Statistical analysis of all results was done using a paired t-test, and p was preset at < 0.05. The logistic regression analysis was performed for cerebral ischemia development dependent on intracranial hypertension and cerebrovascular reactivity. RESULTS: IHT led to an increase in ICP in all the patients, especially during vertical movement in an elevator (maximum 75.2 mm Hg). During the horizontal transportation on the floor, ICP remained increased (p < 0.05). The mean ICP during IHT was significantly higher (26.1 ± 13.5 mm Hg, p < 0.001) than that before the IHT (19.9 ± 5.3 mm Hg). The mean iPRx after and before IHT was 0.52 ± 0.04 and 0.23 ± 0.14, respectively (p < 0.001). CONCLUSIONS: Both horizontal and vertical transportation causes a significant increase in ICP and iPRx in patients with severe TBI, potentially leading to the outcome worsening.

Sex-Specific and Dose-Dependent Effects of Drag-Reducing Polymers on Microcirculation and Tissue Oxygenation in Rats After Traumatic Brain Injury.

Traumatic brain injury (TBI) ultimately leads to a reduction in the cerebral metabolic rate for oxygen due to ischemia. Previously, we showed that 2 ppm i.v. of drag-reducing polymers (DRP) improve hemodynamic and oxygen delivery to tissue in a rat model of mild-to-moderate TBI. Here we evaluated sex-specific and dose-dependent effects of DRP on microvascular CBF (mvCBF) and tissue oxygenation in rats after moderate TBI. In vivo two-photon laser scanning microscopy over the rat parietal cortex was used to monitor the effects of DRP on microvascular perfusion, tissue oxygenation, and blood-brain barrier (BBB) permeability. Lateral fluid-percussion TBI (1.5 ATA, 100 ms) was induced after baseline imaging and followed by 4 h of monitoring. DRP was injected at 1, 2, or 4 ppm within 30 min after TBI. Differences between groups were determined using a two-way ANOVA analysis for multiple comparisons and post hoc testing using the Mann-Whitney U test. Moderate TBI progressively decreased mvCBF, leading to tissue hypoxia and BBB degradation in the pericontusion zone (p < 0.05). The i.v. injection of DRP increased near-wall flow velocity and flow rate in arterioles, leading to an increase in the number of erythrocytes entering capillaries, enhancing capillary perfusion and tissue oxygenation while protecting BBB in a dose-dependent manner without significant difference between males and females (p < 0.01). TBI resulted in an increase in intracranial pressure (20.1 ± 3.2 mmHg, p < 0.05), microcirculatory redistribution to non-nutritive microvascular shunt flow, and stagnation of capillary flow, all of which were dose-dependently mitigated by DRP. DRP at 4 ppm was most effective, with a non-significant trend to better outcomes in female rats.

Low Flow and Microvascular Shunts: A Final Common Pathway to Cerebrovascular Disease: A Working Hypothesis.

Low flow and microvascular shunts (MVS) is the final common pathway in cerebrovascular disease. Low flow in brain capillaries (diam. 3-8 µm) decreases endothelial wall shear rate sensed by the glycocalyx regulating endothelial function: water permeability; nitric oxide synthesis via nitric oxide synthase; leucocyte adhesion to the endothelial wall and penetration into the tissue; activation of cytokines and chemokines initiating inflammation in tissue. Tissue edema combined with pericyte and astrocyte capillary constriction increases capillary resistance. Increased capillary resistance diverts flow through MVS (diam. 10-25 µm) that are non-nutritive, without gas exchange, waste or metabolite clearance and cerebral blood flow (CBF) regulation. MVS predominate in subcortical and periventricular white matter. The shift in flow from capillaries to MVS is a pathological, maladaptive process. Low perfusion in the injured tissue exacerbates brain edema. Low blood flow and MVS alone can lead to all of the processes involved in tissue injury including inflammation and microglial activation.

Cerebrovascular Reserve (CVR) and Stages of Hemodynamic Compromise.

The concept of hemodynamic compromise (HC) is used to detect brain regions under ischemic stress by impaired ability to dilate in response to a vasodilatory challenge for cerebrovascular reserve (CVR). The vasodilatory challenges are either inhaled CO2 or a carbonic anhydrase inhibitor acetazolamide (AZ) with measurements of cerebral blood flow (CBF) before and during the challenge. The rationale for CVR is that the brain under ischemic stress is vasodilated and the increase in CBF is attenuated. However, regional oxygen extraction fraction (OEF) by positron emission tomography (PET) is the gold standard for measurement of HC. We showed a strong correlation between CVR and OEF and the OEF response (OEFR) before and after vasodilation in patients with acute ischemic stroke. These observations suggest that CVR measurements alone identify brain regions under ischemic stress without the need for expensive, time consuming and difficult PET OEF.

Near-Infrared Spectroscopy (NIRS) of Muscle HbO2 and MbO2 Desaturation During Exercise.

Continuous noninvasive monitoring of muscle oxygenation has important clinical applications for muscle disorders such as compartmentation syndrome, fibromyalgia, deep vein thrombosis, malignant hyperthermia, and the assessment of training in athletic performance. NIRS has precisely such potential and has been used to detect deep venous thrombosis, evaluate athletic performance, and assess limb reperfusion and revascularization. The aim of this study was to examine the relationship between muscle hemoglobin oxygen (HbO2) and myoglobin (MbO2) desaturation using NIRS combined with venous blood sampling and HbO2 desaturation during forearm muscle exercise. Eleven normal subjects were studied, with informed consent and an IRB-approved protocol. A NIRS sensor (INVOS4100, Somanetics, Corp.) was applied on the volar aspect of the forearm. The subjects exercised their forearm by clenching and relaxing their fist while observing the oximeter and driving the reading to specified levels from 90% to 15% (minimum possible reading). Venous blood samples were withdrawn for measurement of blood gases and oxygen saturation (IL-Co-Oximeter). RSO2 (%) vs VO2 Sat showed a two-component HbO2 desaturation suggesting representation of venous HbO2 desaturation and perhaps myoglobin oxygen (MBO2) desaturation. Subtraction of the linear venous HbO2 curve from the two-component curve suggests MbO2 desaturation at venous hemoglobin oxygen saturation of about 10-20%. Conclusions: The kinetics of desaturation during exercise revealed two components representing HbO2 and MbO2 deoxygenation. The data show that MbO2 represents approximately 40% of the NIRS signal and the balance or 60% to HbO2.

Cerebral Spreading Depression Transient Disruption of Cross-Frequency Coupling in the Rat Brain: Preliminary Observations.

Normal brain function requires an integrated, simultaneous communication between brain regions in a coordinated manner. In our studies on cortical spreading depolarization (CSD) induced electrically in the rat brain while recording electrocorticography (ECoG) and delta wave activity, we found for the first time that CSD suppressed delta wave activity, which began even before the CSD was fully developed. We pursued this observation to determine whether repeated CSD suppressed delta wave activity in rats. CSD was produced by electrical stimulation of the neocortex while recording the development of CSD and changes in the coupling of low-frequency band cross coupling to four typical physiological neuronal activity frequency bands, i.e., 5-7 Hz, 8-12 Hz, 13-30 Hz, and 30-80 Hz. Band-pass filters were applied to achieve the corresponding physiological band signals. Besides the cross-frequency coupling (CFC) analysis, the distribution of delta wave density in time domain was analyzed. We calculated the delta wave density per 30 seconds but represent the density as frequency per minute. A Generalized Linear Models (GLM) was used to carry out the CFC analysis in Matlab. Because delta waves dominated the ECoG recorded, we modeled the higher-frequency amplitude envelope as a function of low-frequency phase using a spline basis. Besides the CFC analysis, we also characterized the distribution of the delta wave density in time domain. Four CFC, Theta, Alpha, Beta, and Gamma were at very small values after CSD, and after about 8 minutes, the CFC recovered to the pre-CSD level. CFC were seen to decrease before a CSD occurred at the higher-frequency bands and tended to decrease quickly. Whether the attenuated CFC by CSD has long-term consequences remains to be determined. Future studies will explore the impact of cortical CSD on CFC with deeper brain structures, including the thalamus and the caudate putamen.

Addition of Drag-Reducing Polymers to Colloid Resuscitation Fluid Enhances Cerebral Microcirculation and Tissue Oxygenation After Traumatic Brain Injury Complicated by Hemorrhagic Shock.

Hemorrhagic shock (HS) is a severe complication of traumatic brain injury (TBI) that doubles mortality due to severely compromised microvascular cerebral blood flow (mvCBF) and oxygen delivery reduction, as a result of hypotension. Volume expansion with resuscitation fluids (RF) for HS does not improve microvascular CBF (mvCBF); moreover, it aggravates brain edema. We showed that the addition of drag-reducing polymers (DRP) to crystalloid RF (lactated Ringer's) significantly improves mvCBF, oxygen supply, and neuronal survival in rats suffering TBI+HS. Here, we compared the effects of colloid RF (Hetastarch) with DRP (HES-DRP) and without (HES). Fluid percussion TBI (1.5 ATA, 50 ms) was induced in rats and followed by controlled HS to a mean arterial pressure (MAP) of 40 mmHg. HES or HES-DRP was infused to restore MAP to 60 mmHg for 1 h (prehospital period), followed by blood reinfusion to a MAP of 70 mmHg (hospital period). In vivo two-photon microscopy was used to monitor cerebral microvascular blood flow, tissue hypoxia (NADH), and neuronal necrosis (i.v. propidium iodide) for 5 h after TBI+HS, followed by postmortem DiI vascular painting. Temperature, MAP, blood gases, and electrolytes were monitored. Statistical analyses were done using GraphPad Prism by Student's t-test or Kolmogorov-Smirnov test, where appropriate. TBI+HS compromised mvCBF and tissue oxygen supply due to capillary microthrombosis. HES-DRP improved mvCBF and tissue oxygenation (p < 0.05) better than HES. The number of dead neurons in the HES-DRP was significantly less than in the HES group: 76.1 ± 8.9 vs. 178.5 ± 10.3 per 0.075 mm3 (P < 0.05). Postmortem visualization of painted vessels revealed vast microthrombosis in both hemispheres that were 33 ± 2% less in HES-DRP vs. HES (p < 0.05). Thus, resuscitation after TBI+HS using HES-DRP effectively restores mvCBF and reduces hypoxia, microthrombosis, and neuronal necrosis compared to HES. HES-DRP is more neuroprotective than lactated Ringer's with DRP and requires an infusion of a smaller volume, which reduces the development of hypervolemia-induced brain edema.

Improved Cerebral Perfusion Pressure and Microcirculation by Drag Reducing Polymer-Enforced Resuscitation Fluid After Traumatic Brain Injury and Hemorrhagic Shock.

Hemorrhagic shock (HS) after traumatic brain injury (TBI) reduces cerebral perfusion pressure (CPP) and cerebral blood flow (CBF), increasing hypoxia and doubling mortality. Volume expansion with resuscitation fluids (RFs) for HS does not improve CBF and tissue oxygen, while hypervolemia exacerbates brain edema and elevates intracranial pressure (ICP). We tested whether drag-reducing polymers (DRPs), added to isotonic Hetastarch (HES), would improve CBF but prevent ICP increase. TBI was induced in rats by fluid percussion, followed by controlled hemorrhage to mean arterial pressure (MAP) = 40 mmHg. HES-DRP or HES was infused to MAP = 60 mmHg for 1 h, followed by blood reinfusion to MAP = 70 mmHg. Temperature, MAP, ICP, cortical Doppler flux, blood gases, and electrolytes were monitored. Microvascular CBF, tissue hypoxia, and neuronal necrosis were monitored by two-photon laser scanning microscopy 5 h after TBI/HS. TBI/HS reduced CPP and CBF, causing tissue hypoxia. HES-DRP (1.9 ± 0.8 mL) more than HES (4.5 ± 1.8 mL) improved CBF and tissue oxygenation (p < 0.05). In the HES group, ICP increased to 23 ± 4 mmHg (p < 0.05) but in HES-DRP to 12 ± 2 mmHg. The number of dead neurons, microthrombosis, and the contusion volume in HES-DRP were significantly less than in the HES group (p < 0.05). HES-DRP required a smaller volume, which reduced ICP and brain edema.

Resuscitation with Drag Reducing Polymers after Traumatic Brain Injury with Hemorrhagic Shock Reduces Microthrombosis and Oxidative Stress.

Outcome after traumatic brain injury (TBI) is worsened by hemorrhagic shock (HS); however, the existing volume expansion approach with resuscitation fluids (RF) is controversial as it does not adequately alleviate impaired microvascular cerebral blood flow (mCBF). We previously reported that resuscitation fluid with drag reducing polymers (DRP-RF) improves CBF by rheological modulation of hemodynamics. Here, we evaluate the efficacy of DRP-RF, compared to lactated Ringers resuscitation fluid (LR-RF), in reducing cerebral microthrombosis and reperfusion mitochondrial oxidative stress after TBI complicated by HS. Fluid percussion TBI (1.5 ATA, 50 ms) was induced in rats and followed by controlled HS to a mean arterial pressure (MAP) of 40 mmHg. DRP-RF or LR-RF was infused to restore MAP to 60 mmHg for 1 h (pre-hospital period), followed by blood re-infusion to a MAP = 70 mmHg (hospital period). In vivo 2-photon laser scanning microscopy over the parietal cortex was used to monitor microvascular blood flow, nicotinamide adenine dinucleotide (NADH) for tissue oxygen supply and mitochondrial oxidative stress (superoxide by i.v. hydroethidine [HEt], 1 mg/kg) for 4 h after TBI/HS, followed by Dil vascular painting during perfusion-fixation. TBI/HS decreased mCBF resulting in capillary microthrombosis and tissue hypoxia. Microvascular CBF and tissue oxygenation were significantly improved in the DRP-RF compared to the LR-RF treated group (p < 0.05). Reperfusion-induced oxidative stress, reflected by HEt fluorescence, was 32 ± 6% higher in LR-RF vs. DRP-RF (p < 0.05). Post-mortem whole-brain visualization of DiI painted vessels revealed multiple microthromboses in both hemispheres that were 29 ± 3% less in DRP-RF vs. LR-RF group (p < 0.05). Resuscitation after TBI/HS using DRP-RF effectively restores mCBF, reduces hypoxia, microthrombosis formation, and mitochondrial oxidative stress compared to conventional volume expansion with LR-RF.

Anodal Transcranial Direct Current Stimulation Improves Impaired Cerebrovascular Reactivity in Traumatized Mouse Brain.

Cerebrovascular reactivity (CVR) is a compensatory mechanism where blood vessels dilate in response to a vasodilatory stimulus, and is a biomarker of vascular reserve and microvascular health. Impaired CVR indicates microvascular hemodynamic dysfunction, which is implicated in traumatic brain injury (TBI) and associated with long-term neurological deficiency. Recently we have shown that anodal transcranial direct current stimulation (tDCS) caused prolonged dilatation of cerebral arterioles that increased brain microvascular flow and tissue oxygenation in traumatized mouse brain and was associated with neurologic improvement. Here we evaluate the effects of tDCS on impaired CVR and microvascular cerebral blood flow (mCBF) regulation after TBI. TBI was induced in mice by controlled cortical impact (CCI). Cortical microvascular tone, mCBF, and tissue oxygen supply (by nicotinamide adenine dinucleotide, NADH) were measured by two-photon laser scanning microscopy before and after anodal tDCS (0.1 mA/15 min). CVR and mCBF regulation were evaluated by measuring changes in arteriolar diameters and NADH during hypercapnia test before and after tDCS. Transient hypercapnia was induced by 60-s increase of CO2 concentration in the inhalation mixture to 10%. As previously, anodal tDCS dilated arterioles which increased arteriolar blood flow volume that led to an increase in capillary flow velocity and the number of functioning capillaries, thereby improving tissue oxygenation in both traumatized and sham animals. In sham mice, transient hypercapnia caused transient dilatation of cerebral arterioles with constant NADH, reflecting intact CVR and mCBF regulation. In TBI animals, arteriolar dilatation response to hypercapnia was diminished while the NADH level increased (tissue oxygen supply decreased), reflecting impaired CVR and mCBF regulation. Anodal tDCS enhanced reactivity in parenchymal arterioles in both groups (especially in TBI mice) and restored CVR thereby prevented the reduction in tissue oxygen supply during hypercapnia. CVR has been shown to be related to nitric oxide elevation due to nitric oxide synthases activation, which can be sensitive to the electrical field induced by tDCS.

Pulsed Electromagnetic Field (PEMF) Mitigates High Intracranial Pressure (ICP) Induced Microvascular Shunting (MVS) in Rats.

OBJECTIVE: High-frequency pulsed electromagnetic field (PEMF) stimulation is an emerging noninvasive therapy that we have shown increases cerebral blood flow (CBF) and tissue oxygenation in the healthy rat brain. In this work, we tested the effect of PEMF on the brain at high intracranial pressure (ICP). We previously showed that high ICP in rats caused a transition from capillary (CAP) to non-nutritive microvascular shunt (MVS) flow, tissue hypoxia and increased blood brain barrier (BBB) permeability. METHODS: Using in vivo two-photon laser scanning microscopy (2PLSM) over the rat parietal cortex, and studied the effects of PEMF on microvascular blood flow velocity, tissue oxygenation (NADH autofluorescence), BBB permeability and neuronal necrosis during 4 h of elevated ICP to 30 mmHg. RESULTS: PEMF significantly dilated arterioles, increased capillary blood flow velocity and reduced MVS/capillary ratio compared to sham-treated animals. These effects led to a significant decrease in tissue hypoxia, BBB degradation and neuronal necrosis. CONCLUSIONS: PEMF attenuates high ICP-induced pathological microcirculatory changes, tissue hypoxia, BBB degradation and neuronal necrosis.

Induced Dynamic Intracranial Pressure and Cerebrovascular Reactivity Assessment of Cerebrovascular Autoregulation After Traumatic Brain Injury with High Intracranial Pressure in Rats.

OBJECTIVE: In previous work we showed that high intracranial pressure (ICP) in the rat brain induces a transition from capillary (CAP) to pathological microvascular shunt (MVS) flow, resulting in brain hypoxia, edema, and blood-brain barrier (BBB) damage. This transition was correlated with a loss of cerebral blood flow (CBF) autoregulation undetected by static autoregulatory curves but identified by induced dynamic ICP (iPRx) and cerebrovascular (iCVRx) reactivity. We hypothesized that loss of CBF autoregulation as correlated with MVS flow would be identified by iPRx and iCVRx in traumatic brain injury (TBI) with elevated ICP. METHODS: TBI was induced by lateral fluid percussion (LFP) using a gas-driven device in rats. Using in vivo two-photon laser scanning microscopy, cortical microcirculation, tissue oxygenation (NADH autofluoresence), and BBB permeability (fluorescein dye extravasation) were measured before and for 4 h after TBI. Laser Doppler cortical flux, rectal and brain temperature, ICP and mean arterial pressure (MAP), blood gases, and electrolytes were monitored. Every 30 min, a transient 10 mmHg rise in MAP was induced by i.v. bolus of dopamine. iPRx = ΔICP/ΔMAP and iCVRx = ΔCBF/ΔMAP. RESULTS: We demonstrated that iPRx and iCVRx correctly identified more severe loss of CBF autoregulation correlated with a transition of blood flow to MVS after TBI with high ICP compared to TBI without an increase in ICP. CONCLUSIONS: In TBI with high ICP, high-velocity MVS flow is responsible for the loss of CBF autoregulation identified by iPRx and iCVRx.

Effect of Cerebrospinal Fluid Drainage on Brain Tissue Oxygenation in Traumatic Brain Injury.

The effectiveness of cerebrospinal fluid (CSF) drainage in lowering high intracranial pressure (ICP) is well established in severe traumatic brain injury (TBI). Recently, however, the use of external ventricular drains (EVDs) and ICP monitors in TBI has come under question. The aim of this retrospective study was to investigate the effect of CSF drainage on brain tissue oxygenation (PbtO2). Using a multi-modality monitoring system, we continuously monitored PbtO2 and parenchymal ICP during CSF drainage events via a ventriculostomy in 40 patients with severe TBI. Measurements were time-locked continuous recordings on a Component Neuromonitoring System in a neuroscience intensive care unit. We further selected for therapeutic CSF drainage events initiated at ICP values above 25 mm Hg and analyzed the 4-min periods before and after drainage for the physiologic variables ICP, cerebral perfusion pressure (CPP), and PbtO2. We retrospectively identified 204 CSF drainage events for ICP EVD-opening values greater than 25 mm Hg in 23 patients. During the 4 min of opened EVD, ICP decreased by 5.7 ± 0.6 mm Hg, CPP increased by 4.1 ± 1.2 mm Hg, and PbtO2 increased by 1.15 ± 0.26 mm Hg. ICP, CPP, and PbtO2 all improved with CSF drainage at ICP EVD-opening values above 25 mm Hg. Although the average PbtO2 changes were small, a clinically significant change in PbtO2 of 5 mm Hg or greater occurred in 12% of CSF drainage events, which was correlated with larger decreases in ICP, displaying a complex relationship between ICP and PbtO2 that warrants further studies.

Rheological effects of drag-reducing polymers improve cerebral blood flow and oxygenation after traumatic brain injury in rats.

Cerebral ischemia has been clearly demonstrated after traumatic brain injury (TBI); however, neuroprotective therapies have not focused on improvement of the cerebral microcirculation. Blood soluble drag-reducing polymers (DRP), prepared from high molecular weight polyethylene oxide, target impaired microvascular perfusion by altering the rheological properties of blood and, until our recent reports, has not been applied to the brain. We hypothesized that DRP improve cerebral microcirculation and oxygenation after TBI. DRP were studied in healthy and traumatized rat brains and compared to saline controls. Using in-vivo two-photon laser scanning microscopy over the parietal cortex, we showed that after TBI, nanomolar concentrations of intravascular DRP significantly enhanced microvascular perfusion and tissue oxygenation in peri-contusional areas, preserved blood-brain barrier integrity and protected neurons. The mechanisms of DRP effects were attributable to reduction of the near-vessel wall cell-free layer which increased near-wall blood flow velocity, microcirculatory volume flow, and number of erythrocytes entering capillaries, thereby reducing capillary stasis and tissue hypoxia as reflected by a reduction in NADH. Our results indicate that early reduction in CBF after TBI is mainly due to ischemia; however, metabolic depression of contused tissue could be also involved.

Drag-Reducing Polymer Enhances Microvascular Perfusion in the Traumatized Brain with Intracranial Hypertension.

Current treatments for traumatic brain injury (TBI) have not focused on improving microvascular perfusion. Drag-reducing polymers (DRP), linear, long-chain, blood-soluble, nontoxic macromolecules, may offer a new approach to improving cerebral perfusion by primary alteration of the fluid dynamic properties of blood. Nanomolar concentrations of DRP have been shown to improve hemodynamics in animal models of ischemic myocardium and ischemic limb, but have not yet been studied in the brain. We recently demonstrated that DRP improved microvascular perfusion and tissue oxygenation in a normal rat brain. We hypothesized that DRP could restore microvascular perfusion in hypertensive brain after TBI. Using in vivo two-photon laser scanning microscopy we examined the effect of DRP on microvascular blood flow and tissue oxygenation in hypertensive rat brains with and without TBI. DRP enhanced and restored capillary flow, decreased microvascular shunt flow, and, as a result, reduced tissue hypoxia in both nontraumatized and traumatized rat brains at high intracranial pressure. Our study suggests that DRP could constitute an effective treatment for improving microvascular flow in brain ischemia caused by high intracranial pressure after TBI.