The neurophysiological effect of mild hypothermia in gyrencephalic brains submitted to ischemic stroke and spreading depolarizations.

Objective: Characterize the neurophysiological effects of mild hypothermia on stroke and spreading depolarizations (SDs) in gyrencephalic brains. Methods: Left middle cerebral arteries (MCAs) of six hypothermic and six normothermic pigs were permanently occluded (MCAo). Hypothermia began 1 h after MCAo and continued throughout the experiment. ECoG signals from both frontoparietal cortices were recorded. Five-minute ECoG epochs were collected 5 min before, at 5 min, 4, 8, 12, and 16 h after MCAo, and before, during, and after SDs. Power spectra were decomposed into fast (alpha, beta, and gamma) and slow (delta and theta) frequency bands. Results: In the vascular insulted hemisphere under normothermia, electrodes near the ischemic core exhibited power decay across all frequency bands at 5 min and the 4th hour after MCAo. The same pattern was registered in the two furthest electrodes at the 12th and 16th hour. When mild hypothermia was applied in the vascular insulted hemispheres, the power decay was generalized and seen even in electrodes with uncompromised blood flow. During SD analysis, hypothermia maintained increased delta and beta power during the three phases of SDs in the furthest electrode from the ischemic core, followed by the second furthest and third electrode in the beta band during preSD and postSD segments. However, in hypothermic conditions, the third electrode showed lower delta, theta, and alpha power. Conclusion: Mild hypothermia attenuates all frequency bands in the vascularly compromised hemisphere, irrespective of the cortical location. During SD formation, it preserves power spectra more significantly in electrodes further from the ischemic core.

Mild hypothermia reduces spreading depolarizations and infarct size in a swine model.

Spreading depolarizations (SDs) have been linked to infarct volume expansion following ischemic stroke. Therapeutic hypothermia provides a neuroprotective effect after ischemic stroke. This study aimed to evaluate the effect of hypothermia on the propagation of SDs and infarct volume in an ischemic swine model. Through left orbital exenteration, middle cerebral arteries were surgically occluded (MCAo) in 16 swine. Extensive craniotomy and durotomy were performed. Six hypothermic and five normothermic animals were included in the analysis. An intracranial temperature probe was placed right frontal subdural. One hour after ischemic onset, mild hypothermia was induced and eighteen hours of electrocorticographic (ECoG) and intrinsic optical signal (IOS) recordings were acquired. Postmortem, 4 mm-thick slices were stained with 2,3,5-triphenyltetrazolium chloride to estimate the infarct volume. Compared to normothermia (36.4 ± 0.4°C), hypothermia (32.3 ± 0.2°C) significantly reduced the frequency and expansion of SDs (ECoG: 3.5 ± 2.1, 73.2 ± 5.2% vs. 1.0 ± 0.7, 41.9 ± 21.8%; IOS 3.9 ± 0.4, 87.6 ± 12.0% vs. 1.4 ± 0.7, 67.7 ± 8.3%, respectively). Further, infarct volume among hypothermic animals (23.2 ± 1.8% vs. 32.4 ± 2.5%) was significantly reduced. Therapeutic hypothermia reduces infarct volume and the frequency and expansion of SDs following cerebral ischemia.

Cerebrovascular Pressure Reactivity According to Long-Pressure Reactivity Index During Spreading Depolarizations in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Spreading depolarization (SD) has been linked to the impairment of neurovascular coupling. However, the association between SD occurrence and cerebrovascular pressure reactivity as a surrogate of cerebral autoregulation (CA) remains unclear. Therefore, we analyzed CA using the long-pressure reactivity index (L-PRx) during SDs in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: A retrospective study of patients with aSAH who were recruited at two centers, Heidelberg (HD) and Berlin (BE), was performed. Continuous monitoring of mean arterial pressure (MAP) and intracranial pressure (ICP) was recorded. ICP was measured using an intraparenchymal probe in HD patients and was measure in BE patients through external ventricular drainage. Electrocorticographic (ECoG) activity was continuously recorded between 3 and 13 days after hemorrhage. Autoregulation according to L-PRx was calculated as a moving linear Pearson's correlation of 20-min averages of MAP and ICP. For every identified SD, 60-min intervals of L-PRx were averaged, plotted, and analyzed depending on SD occurrence. Random L-PRx recording periods without SDs served as the control. RESULTS: A total of 19 patients (HD n = 14, BE n = 5, mean age 50.4 years, 9 female patients) were monitored for a mean duration of 230.4 h (range 96-360, STD ± 69.6 h), during which ECoG recordings revealed a total number of 277 SDs. Of these, 184 represented a single SD, and 93 SDs presented in clusters. In HD patients, mean L-PRx values were 0.12 (95% confidence interval [CI] 0.11-0.13) during SDs and 0.07 (95% CI 0.06-0.08) during control periods (p < 0.001). Similarly, in BE patients, a higher L-PRx value of 0.11 (95% CI 0.11-0.12) was detected during SDs than that during control periods (0.08, 95% CI 0.07-0.09; p < 0.001). In a more detailed analysis, CA changes registered through an intraparenchymal probe (HD patients) revealed that clustered SD periods were characterized by signs of more severely impaired CA (L-PRx during SD in clusters: 0.23 [95% CI 0.20-0.25]; single SD: 0.09 [95% CI 0.08-0.10]; control periods: 0.07 [95% CI 0.06-0.08]; p < 0.001). This group also showed significant increases in ICP during SDs in clusters compared with single SD and control periods. CONCLUSIONS: Neuromonitoring for simultaneous assessment of cerebrovascular pressure reactivity using 20-min averages of MAP and ICP measured by L-PRx during SD events is feasible. SD occurrence was associated with significant increases in L-PRx values indicative of CA disturbances. An impaired CA was found during SD in clusters when using an intraparenchymal probe. This preliminary study validates the use of cerebrovascular reactivity indices to evaluate CA disturbances during SDs. Our results warrant further investigation in larger prospective patient cohorts.

Serum repressor element-1 silencing transcription factor levels in alzheimer's patients from a national institute of health in mexico city, elderly and young controls

ABSTRACT Background: Decreased levels of repressor element-1 silencing transcription (REST) factor in the brain, plasma, and neuron-derived exosomes are associated with Alzheimer’s disease (AD). Objective: The objective of the study was to test the viability of serum REST as a possible blood-based biomarker for AD, comparing serum REST levels in AD patients from a National Institute of Health in Mexico City (with different levels of severity and comorbidities), with elderly controls (EC) and young controls (YC). Methods: We used an enzyme-linked immunosorbent assay to determine serum REST levels in AD patients (n = 28), EC (n = 19), and YC (n = 24); the AD patients were classified by dementia severity and comorbidities (depression and microangiopathy) using clinimetric tests and magnetic resonance imaging. Results: Mean serum REST levels did not differ between AD patients, EC, and YC. The severity of AD and the presence of depression or microangiopathy were not associated with serum REST levels. Conclusion: Our results differ from previously published patterns found for plasma and cerebral REST levels. Free serum REST levels may not be a viable AD blood-based biomarker. (REV INVEST CLIN. 2021;73(1):17-22)

Serum Repressor Element-1 Silencing Transcription Factor Levels in Alzheimer's Patients from a National Institute of Health in Mexico City, Elderly and Young Controls.

BACKGROUND: Decreased levels of repressor element-1 silencing transcription (REST) factor in the brain, plasma, and neuronderived exosomes are associated with Alzheimer's disease (AD). OBJECTIVE: The objective of the study was to test the viability of serum REST as a possible blood-based biomarker for AD, comparing serum REST levels in AD patients from a National Institute of Health in Mexico City (with different levels of severity and comorbidities), with elderly controls (EC) and young controls (YC). METHODS: We used an enzyme-linked immunosorbent assay to determine serum REST levels in AD patients (n = 28), EC (n = 19), and YC (n = 24); the AD patients were classified by dementia severity and comorbidities (depression and microangiopathy) using clinimetric tests and magnetic resonance imaging. RESULTS: Mean serum REST levels did not differ between AD patients, EC, and YC. The severity of AD and the presence of depression or microangiopathy were not associated with serum REST levels. CONCLUSION: Our results differ from previously published patterns found for plasma and cerebral REST levels. Free serum REST levels may not be a viable AD blood-based biomarker.