Cerebral Microcirculation and Oxygenation Modulation by Transcranial Alternating Current Stimulation in Awake and Anesthetized Mice.

Transcranial alternating current stimulation (tACS) is a novel non-invasive electrical stimulation technique where a sinusoidal oscillating low-voltage electric current is applied to the brain. TACS is being actively investigated in practice for cognition and behavior modulation and for treating brain disorders. However, the physiological mechanisms of tACS are underinvestigated and poorly understood. Previously, we have shown that transcranial direct current stimulation (tDCS) facilitates cerebral microcirculation and oxygen supply in a mouse brain through nitric oxide-dependent vasodilatation of arterioles. Considering that the effects of tACS and tDCS might be both similar and dissimilar, we tested the effects of tACS on regional cerebral blood flow and oxygen saturation in anesthetized and awake mice using laser speckle contrast imaging and multispectral intrinsic optical signal imaging. The anesthetized mice were imaged under isoflurane anesthesia ∼1.0% in 30% O2 and 70% N2O. The awake mice were pre-trained on the rotating ball for awake imaging. Baseline imaging with further tACS was followed by post-stimulation imaging for ~3 h. Differences between groups were determined using a two-way ANOVA analysis for multiple comparisons and post hoc testing using the Mann-Whitney U test. TACS increased cerebral blood flow and oxygen saturation. In awake mice, rCBF and oxygen saturation responses were more robust and prolonged as opposed to anesthetized, where the response was weaker and shorter with overshoot. The significant difference between anesthetized and awake mice emphasizes the importance of the experiments on the latter as anesthesia is not typical for human stimulation and significantly alters the results.

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.

Moderate Severity SARS-CoV-2 (COVID-19) Affects Ocular Vergence Indices: Eye Tracking-Based Study.

OBJECTIVE: Since the start of the SARS-CoV-2 (COVID-19) pandemic, it has become clear that the brain is one of the main targets for acute and chronic damage. Although neurodegenerative changes have yet to be investigated, there is already a large body of data on damage to its fiber tracts. A mobile eye tracker is possibly one of the best tools to study such damage in a COVID hospital setting. At the same time, the available data indicate that eye tracking parameters, even in healthy volunteers, demonstrate a distinct gender-specific difference.The aim of the work is to evaluate functional and structural impairments of the fiber tracts and to find possible gender-specific dynamics of eye tracking indicators in the acute period of COVID-19 pneumonia (Delta variant) of moderate severity. MATERIALS AND METHODS: A single-center non-randomized retrospective study included 84 patients in the acute period of moderate severity SARS-CoV-2 (COVID-19) pneumonia (Delta variant) (Group 1). The mean time from admission was 1.4 ± 1.2 days. M:41, F:43. According to thoracic CT, the lung involvement ranged from CT 1 to CT 2. SpO2 ranged from 95% to 99%. The mean age was 35.5 ± 14.8 years (from 18 to 60). The control group (Group 2) included 158 healthy volunteers without pathology of the vision organs and central nervous system.The eye vergence index (VRx) was determined using eye tracking as a motion correlation coefficient between the angular velocities of the left and right eyeballs and was a measure of the conjugation of horizontal and vertical eye movements.The mobile complex Eye Tracker Low-Speed 20 (BVG LLC, the Netherlands) was used. Eye tracking parameters were assessed by vertical and horizontal eye vergence (VVRx and HVRx).Statistical analysis was done using the methods of parametric and non-parametric statistics. RESULTS: Moderate COVID-19 pneumonia resulted in a significant decrease in both VVRx and HVRx compared to controls (0.763 ± 0.127 and 0.856 ± 0.043; p < 0.000001; 0.729 ± 0.018 and 0.776 ± 0.023 p < 0.000001, respectively). VVRx values were significantly higher in men (0.775 ± 0.046 and 0.747 ± 0.091, p = 0.019, respectively), while Ð¥VRx values were significantly higher in women (0.665 ± 0.018 and 0.728 ± 0.024, p < 0.0000001, respectively). CONCLUSIONS: SARS-CoV-2 (COVID-19) of moderate severity is accompanied by a significant deterioration in eye tracking performance proving functional and structural impairments (p < 0.05). VVRx was significantly higher in men, and HVRx was substantially greater in women reflecting gender-specific differences.

Changes of Arterial and Venous Cerebral Blood Flow Correlation in Moderate-to-Severe Traumatic Brain Injury: A CT Perfusion Study.

We compared differences in perfusion computed tomography (PCT)-derived arterial and venous cerebral blood flow (CBF) in moderate-to-severe traumatic brain injury (TBI) as an indication of changes in cerebral venous outflow patterns referenced to arterial inflow. 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 (diffuse severe TBI after the surgery). Arterial and venous CBF was measured by PCT in both the middle cerebral arteries (CBFmca) and the upper sagittal sinus (CBFuss). In group I, CBFmca on the left and right sides were significantly correlated with each other (p < 0.0001) and with CBFuss (p = 0.048). In group II, CBFmca on the left and right sides were also correlated (p < 0.0000001) but not with CBFuss. Intracranial pressure reactivity (PRx) and CBFuss were correlated (p = 0.00014). In group III, CBFmca on the side of the removed hematoma was not significantly different from the opposite CBFmca (p = 0.680) and was not correlated with CBFuss. Conclusions: The increasing severity of TBI is accompanied by an impairment of the correlation between the arterial and venous CBF in the supratentorial vessels suggesting shifting in arterial and venous CBF in severe TBI associated with increased ICP reflected by PRx.

Cerebral Net Water Uptake in Posttraumatic Cerebral Ischemia.

We assessed net water uptake changes (NWU) in regions of posttraumatic ischemia in relation to cerebral microcirculation mean transit time (MTT) at moderate-to-severe traumatic brain injury (TBI). MATERIALS AND METHODS: 128 moderate-to-severe traumatic brain injury patients (44 women, 84 men, age: 37 ± 12 years) were stratified into 3 groups: Marshall 2-3: 48 patients, Marshall 4: 44 patients, Marshall 5: 36 patients. The groups were matched by sex and age. Patients received multiphase perfusion computed tomography (PCT) 1-5 days after admission. Net water uptake was calculated from non-contrast computed tomography. Data are shown as a median [interquartile range]. P < 0.05 was considered statistically significant. RESULTS: Cerebral blood flow in posttraumatic ischemia foci in Marshall 4 group was significantly higher than that in the Marshall 5 group (p = 0.027). Net water uptake in posttraumatic ischemia zones was significantly higher than in zones without posttraumatic ischemia (8.1% versus 4.2%, p < 0.001). Mean transit time in posttraumatic ischemia zones was inversely and significantly correlated with higher net water uptake (R2 = 0,089, p < 0.01). CONCLUSIONS: Delay of blood flow through the cerebral microvascular bed was significantly correlated with the increased net water uptake in posttraumatic ischemia foci. Marshall's classification did not predict the progression of posttraumatic ischemia.

Involvement of Endothelial Nitric Oxide Synthase in Cerebral Microcirculation and Oxygenation in Traumatic Brain Injury.

Traumatic brain injury (TBI) leads to cerebral microvascular dysfunction and cerebral ischemia. Endothelial nitric oxide synthase (eNOS) is a key regulator of vascular homeostasis. We aimed to assess the role of eNOS in cerebral blood flow (CBF) changes after TBI. Moderate TBI was induced in eNOS knockout (KO) and wild-type (WT) mice (8 per group). Cerebral microvascular tone, microvascular CBF (mCBF) and tissue oxygenation (NADH) were measured by two-photon laser scanning microscopy (2PLSM) before and 1 h, 1 day and 3 days after TBI. Cerebrovascular reactivity (CVR) was evaluated by the hypercapnia test. Laser Doppler cortical flux (cLDF) was simultaneously measured in the perilesional area. One hr after TBI, cLDF was 59.4 ± 8.2% and 60.3 ± 9.1% from the baseline (p < 0.05) in WT and eNOS KO, respectively. 2PLSM showed decreased arteriolar diameter, the number of functioning capillaries, mCBF and tissue oxygenation (p < 0.05). At 1 day, cLDF increased to 65.2 ± 6.4% in the WT group, while it decreased to 56.1 ± 7.2% in the eNOS KO mice. 2PLSM revealed a further decrease in the number of functioning capillaries, mCBF, and oxygen supply which was slightly milder in WT mice (p < 0.05 from the baseline). On the third day after TBI, cLDF increased to 72 ± 5.2% in the WT, while it stayed the same in the eNOS KO group (55.9 ± 6.4%, p < 0.05 from the WT). 2PLSM showed reduction in arterioles with vasospasm, increase in the number of functioning capillaries, and improvement in mCBF and tissue oxygen supply in WT, while no significant changes were observed in eNOS KO (p < 0.05). CVR was impaired in both groups 1 h after TBI, and improved by the third day in the WT, while staying impaired in eNOS KO. In the subacute TBI period, the significance of eNOS in maintaining cerebral microcirculation and oxygen supply increases with time after the injury.

NIRS-Based Study of Local Cerebral Oxygenation During Transcranial Direct Current Stimulation in Patients with Mild Traumatic Brain Injury.

The purpose of our study was to assess the dynamics of local cerebral oxygenation (LCO) by near-infrared spectroscopy (NIRS) during transcranial direct current stimulation (tDCS) in the acute stage of mild traumatic brain injury (mTBI). Fifty-seven mTBI patients (18 women and 39 men, 35 ± 11.7 years old, GCS 13.7 ± 0.7) were treated by tDCS at 3-5 days after head injury. Stimulation parameters were: 1 mA, 9 V, duration-20 min. A cerebral oximeter was used to assess LCO-values in the frontotemporal lobes. Anodal and cathodal LCO values were compared before tDCS and every 2 min until the tDCS end. Significance was preset to p < 0.05. Results: A significant decrease in LCO values on the anodal side was observed at the 8th to 12th minutes of stimulation, compared to the cathodal side (at 8th minute - p = 0.011; at 12th minute - p < 0.00000001) and compared to LCO values before tDCS (p < 0.00001). The LCO on the cathodal side was not significantly different during the whole tDCS. At the end of the procedure, the interhemispheric LCO differences were not statistically significant (p = 0.757). Conclusions: Transcranial DCS in 3-5 days of mTBI leads to a significant decrease in the LCO value on the anodal side between 8 and 12 min and subsequent recovery to baseline values by the end of the procedure.

Critical Closing Pressure of Cerebral Circulation at Concomitant Moderate-to-Severe Traumatic Brain Injury.

BACKGROUND: Critical closing pressure (CrCP) is the pressure below which local pial blood pressure is inadequate to prevent blood flow cessation. The state of cerebral CrCP in patients with concomitant moderate-to-severe traumatic brain injury (cTBI) after brain lesions surgery remains poorly understood. AIM: The aim of our study was to establish the dynamics of CrCP after intracranial surgery in traumatic brain injury (TBI) patients with polytrauma. MATERIAL AND METHODS: Results of the treatment of 70 patients with moderate-to-severe сTBI were studied (Male: Female - 39:31, mean age -33.2 ± 12.2 years). Depending on intracranial surgery, patients were divided into 2 groups. All patients were subjected to transcranial Doppler of both middle cerebral arteries, and evaluation of mean arterial pressure (MAP). Based on the data obtained, CrCPs were calculated. Significance was preset to P < 0.05. RESULTS: Mean CrCP values in each group were significantly higher than a reference range (р < 0.01). There was no significant difference in CrCP values between the left and right hemispheres in the group 1 (p = 0.789). In the group 2, mean CrCP values on the unoperated side remained significantly lower than on the operated side (p = 0.000011) even after intracranial surgery. In group 1, mean CrCP values were significantly lower than on the surgery side in the group 1 (Z = 3,4; р = 0.043). CONCLUSION: CrCP values in concomitant moderate-to-severe TBI after removing brain lesions and without surgery were significantly higher than referral data. Even after removal of brain lesions volumes in patients with concomitant moderate-to-severe TBI, CrCP values on the surgery side remained markedly higher than on the side opposite to the removed lesion volumes.

Cerebral Critical Closing Pressure in Concomitant Traumatic Brain Injury and Intracranial Hematomas.

The critical closing pressure (CrCP) is the pressure below which the local pial blood pressure is inadequate to prevent blood flow cessation. The cerebral CrCP in concomitant traumatic brain injury (TBI) and intracranial hematomas (TBI + ICH) remains understudied. The aim was to determine the status of the CrCP at сTBI with and without the ICH development. MATERIAL AND METHODS: The results of the treatment of 90 patients with severe to moderate сTBI were studied (male/female - 49:41). The average age was 34.2 ± 14.4 years. Depending on the presence of ICH, patients were divided into two groups. All patients were subjected to transcranial Doppler of the both middle cerebral arteries, and evaluation of mean arterial pressure (MAP). Based on data obtained, the CrCPs were calculated. Significance was preset to p < 0.05. RESULTS: The mean CrCP values in each group appeared to be significantly higher than a referral value (р < 0.05). The mean CrCP values in the perifocal zone of removed hematoma were significantly higher than in TBI patients without ICH (р = 0.015 and р = 0.048, respectively). Analysis of CrCP values in various types of ICH showed no statistically significant differences (р > 0.05). DISCUSSION: The CrCP significantly differs in the groups of TBI patients with and without ICH. The comparability of the groups in respect to the concomitant injury structure proves that the revealed CrCP changes result from the traumatic compression of the brain.

The Changes in Brain Oxygenation During Transcranial Alternating Current Stimulation as Consequences of Traumatic Brain Injury: A Near-Infrared Spectroscopy Study.

The aim was to evaluate the changes in brain tissue oxygenation, assessed by near-infrared spectroscopy (NIRS), during transcranial alternating current stimulation (tACS) in patients with mild and moderate traumatic brain injury (TBI). Nineteen patients with diffuse, blunt, non-severe TBI (mean age 32.7 ± 11.4 years; 4 women and 15 men; Glasgow Coma Score before tACS 14.1 ± 0.5) were treated by 10 Hz in-phase tACS applied for 30 minutes to the left and right lateral prefrontal cortex at 21 days after TBI. Regional cerebral tissue oxygen saturation (SctO2) in the frontal lobes was measured simultaneously by the cerebral oximeter. Significance was preset to P < 0.05. The SctO2 values before tACS were not different between hemispheres ~65%. After 15 minutes of tACS, a significant (p < 0.05) decrease in regional SctO2 was observed with the minimum at the eighth minute of 53.4 ± 3.2% and 53.4 ± 3.2% in the left and right hemispheres, respectively. At the end of the stimulation (30 minutes), the hemispheric differences in cerebral oxygen saturation became statistically insignificant again (p > 0.05). Therefore, tACS causes a significant decrease in SctO2, probably, due to neuronal activation. Our data indicate that tACS may need to be supplemented with oxygen therapy. Further research is required.

NIRS-Based Assessment of Cerebral Oxygenation During High-Definition Anodal Transcranial Direct Current Stimulation in Patients with Posttraumatic Encephalopathy.

The aim was to evaluate the changes in brain tissue oxygenation, assessed by near-infrared spectroscopy (NIRS) during high-definition transcranial direct current stimulation (HD-tDCS) in patients with posttraumatic encephalopathy (PTE). Fifty-two patients with PTE after diffuse, blunt, non-severe traumatic brain injury (TBI) (14 women and 38 men, 31.8 ± 12.5 years, Glasgow Coma Score before tDCS 13.2 ± 0.3) were treated with HD-tDCS at 21 days after TBI. The parameters were as follows: 1 mA, 9 V, and current density ~0.15 mA/cm2. The duration of HD-tDCS was 30 min. The anodal and cathodal electrodes were placed over the left M1 and contralateral supraorbital region, respectively. HD-tDCS was delivered by a direct current stimulator with a pair of surface sponge electrodes (S = 3 cm2). Regional cerebral oxygen saturation (SctO2) in the frontal lobes was measured simultaneously and bilaterally by the cerebral oximeter. SctO2 values were compared before stimulation, by the 15th minute and at the end of the tDCS. Significance was preset to p < 0.05. Results. Before the stimulation, SctO2 values varied between 53% and 86% (74 ± 7.1%) without significant difference between hemispheres (p = 0.135). After 15 min, a significant (p < 0.0000001) decrease in regional SctO2 on the anodal side was observed (mean 54.5 ± 5.6%). On the cathodal side, SctO2 remained unchanged. At the end of the stimulation (30 min), differences between the hemispheres in SctO2 remained statistically significant (p < 0.05). Conclusions. In patients with PTE complicated by TBI, HD-tDCS causes a statistically significant (p < 0.05) decrease in regional SctO2 on the anodal side.

The Cerebrovascular Resistance in Combined Traumatic Brain Injury with Intracranial Hematomas.

OBJECTIVE: The aim was to evaluate changes in cerebrovascular resistance (CVR) in combined traumatic brain injury (CTBI) in groups with and without intracranial hematomas (IH). MATERIALS AND METHODS: Treatment outcomes in 70 patients with CTBI (42 males and 28 females) were studied. Mean age was 35.5 ± 14.8 years (range, 15-73). The patients were divided into two groups: group 1 included 34 CTBI patients without hematomas; group 2 comprised 36 patients with CTBI and IH. The severity according to the Glasgow Coma Scale averaged 10.4 ± 2.6 in group 1, and 10.6 ± 2.8 in group 2. All patients underwent perfusion computed tomography (CT) and transcranial Doppler of both middle cerebral arteries. Cerebral perfusion pressure and CVR were calculated. RESULTS: The mean CVR values in each group (both with and without hematomas) appeared to be statistically significantly higher than the mean normal value. Intergroup comparison of CVR values showed statistically significant increase in the CVR level in group 2 on the side of the removed hematoma (р = 0.037). CVR in the perifocal zone of the removed hematoma remained significantly higher compared with the symmetrical zone in the contralateral hemisphere (p = 0.0009). CONCLUSION: CVR in patients with CTBI is significantly increased compared to the normal value and remains elevated after evacuation of hematoma in the perifocal zone compared to the symmetrical zone in the contralateral hemisphere. This is indicative of certain correlation between the mechanisms of cerebral blood flow autoregulation and maintaining CVR.

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.