DIY caging apparatus to facilitate chronic and continuous stimulation or recording in an awake rodent

Chronic stimulation of and recording from the brain and brain diseases can require expensive apparatus and tedious cycles of inducing rodents with anesthesia. To resolve this, we have designed and fabricated a low-cost (~$75 vs. $450) DIY rodent caging apparatus consisting of commercially available and 3D-printed components. This apparatus is customizable and can be used to rapidly prototype devices with large rodent sample sizes. Importantly, it enables continuous and chronic stimulation of and recording from the brains of awake and freely moving rodents. It also opens the possibilities of trying complex paradigms of treatment (continuous, intermittent, variable, and chronic). We have successfully used this caging apparatus for chronic intratumoral hypothermia treatment and are currently using it while advancing electrotactic therapies.

Decreased Intracranial Pressure Elevation and Cerebrospinal Fluid Outflow Resistance: A Potential Mechanism of Hypothermia Cerebroprotection Following Experimental Stroke

Background: Elevated intracranial pressure (ICP) occurs 18–24 h after ischaemic stroke and is implicated as a potential cause of early neurological deterioration. Increased resistance to cerebrospinal fluid (CSF) outflow after ischaemic stroke is a proposed mechanism for ICP elevation. Ultra-short duration hypothermia prevents ICP elevation 24 h post-stroke in rats. We aimed to determine whether hypothermia would reduce CSF outflow resistance post-stroke. Methods: Transient middle cerebral artery occlusion was performed, followed by gradual cooling to 33 °C. At 18 h post-stroke, CSF outflow resistance was measured using a steady-state infusion method. Results: Hypothermia to 33 °C prevented ICP elevation 18 h post-stroke (hypothermia ∆ICP = 0.8 ± 3.6 mmHg vs. normothermia ∆ICP = 4.4 ± 2.0 mmHg, p = 0.04) and reduced infarct volume 24 h post-stroke (hypothermia = 78.6 ± 21.3 mm3 vs. normothermia = 108.1 ± 17.8 mm3; p = 0.01). Hypothermia to 33 °C did not result in a significant reduction in CSF outflow resistance compared with normothermia controls (0.32 ± 0.36 mmHg/µL/min vs. 1.07 ± 0.99 mmHg/µL/min, p = 0.06). Conclusions: Hypothermia treatment was protective in terms of ICP rise prevention, infarct volume reduction, and may be implicated in CSF outflow resistance post-stroke. Further investigations are warranted to elucidate the mechanisms of ICP elevation and hypothermia treatment.

Mammillary body injury in neonatal encephalopathy: a multicentre, retrospective study

Background The mammillary bodies (MBs) have repeatedly been shown to be critical for memory, yet little is known about their involvement in numerous neurological conditions linked to memory impairments, including neonatal encephalopathy. Methods We implemented a multicentre retrospective study, assessing magnetic resonance scans of 219 infants with neonatal encephalopathy who had undergone hypothermia treatment in neonatal intensive care units located in the Netherlands and Italy. Results Abnormal MB signal was observed in ~40% of infants scanned; in half of these cases, the brain appeared otherwise normal. MB involvement was not related to the severity of encephalopathy or the pattern/severity of hypoxic–ischaemic brain injury. Follow-up scans were available for 18 cases with abnormal MB signal; in eight of these cases, the MBs appeared severely atrophic. Conclusions This study highlights the importance of assessing the status of the MBs in neonatal encephalopathy; this may require changes to scanning protocols to ensure that the slices are sufficiently thin to capture the MBs. Furthermore, long-term follow-up of infants with abnormal MB signal is needed to determine the effects on cognition, which may enable the use of early intervention strategies. Further research is needed to assess the role of therapeutic hypothermia in MB involvement in neonatal encephalopathy. Impact The MBs are particularly sensitive to hypoxia in neonates. Current hypothermia treatment provides incomplete protection against MB injury. MB involvement is likely overlooked as it can often occur when the rest of the brain appears normal. Given the importance of the MBs for memory, it is necessary that this region is properly assessed in neonatal encephalopathy. This may require improvements in scanning protocols.

Analysis of Risk Factors for Early-onset Ventilator-associated Pneumonia in a Neurosurgical Intensive Care Unit: A Single-center Retrospective Study

Background:Ventilator-associated pneumonia (VAP) is a severe infection among patients in the neurosurgery intensive care unit (NICU).Methods:We retrospectively evaluated risk factors for early-onset ventilator-associated pneumonia (EOVAP) from January 2019 to December 2019 at a NICU. A total of 89 NICU patients who were intubated within 48 hours of onset and whose mechanical ventilation time was longer than 7 days were enrolled. The enrolled patients had no history of chronic lung disease and no clinical manifestations of infection before intubation. Clinical data of patients were recorded, and the incidence of and risk factors for EOVAP were analyzed. Patients were also grouped by age (≥65 vs. <65 years) and whether they had received hypothermia treatment or not.Results:Among 89 mechanically ventilated patients (49 men and 40 women; median age 60.1±14.3 years), 40 patients (44.9%) developed EOVAP in 7 days and 14 patients (15.7%) had multidrug resistant bacteria. Binary logistic regression analysis indicated that older age (≥65years) (odds ratio [OR]: 0.267, 95% confidence interval [CI]: 0.101-0.709, P=0.008) and therapeutic hypothermia (OR: 0.235, CI: 0.075-0.738, p=0.013) were independent predictors of EOVAP. Levels of peripheral blood leukocytes, neutrophils and platelets were lower in the therapeutic hypothermia group than those that did not receive hypothermia treatment.Conclusions:This study found that older age (≥65years) and therapeutic hypothermia were independently associated with the risk of EOVAP in NICU patients.

The Diagnostic Value of Cystatin C and Mild Hypothermia Therapy Based on Immunoturbidimetry Enhanced by Nanospheres in Asphyxia Neonate

In order to evaluate the early diagnosis value of CysC and the influence of mild hypothermia on the renal damage of asphyxia neonates, the serum cystatin C (CysC) levels of asphyxia neonates and normal neonates were measured by the nanomicrosphere-enhanced immunoturbidimetric method. The treatment was carried out, and the influence of mild hypothermia treatment on the renal damage of asphyxia neonates was analyzed. The results showed that the indicators of the asphyxia group were significantly higher than those of the control group, and the severe asphyxia group was significantly higher than that of the mild asphyxia group, which was statistically significant p < 0.05 ; the heart rate of patients in the mild hypothermia treatment group decreased gradually with the decrease in body temperature. And compared with the control group, there was a significant difference ( p < 0.05 ); after symptomatic treatment, the two groups of ALT, AST, BUN, and SCR were improved to varying degrees, and the difference was statistically significant compared with before treatment ( p < 0.05 ). Studies have shown that serum CysC level can be used as an indicator to detect glomerular filtration function and early asphyxia newborns, and it is sensitive and specific for early diagnosis of kidney damage. At the same time, it can be used to monitor clinical renal function and determine the status of asphyxia newborns.

Monitoring the effectiveness of hypothermia in perinatal asphyxia infants by urinary S100B levels

Background Perinatal asphyxia is a major cause of mortality and morbidity in neonates: The aim of the present study was to investigate, by means of longitudinal assessment of urinary S100B, the effectiveness of hypothermia, in infants complicated by perinatal asphyxia and hypoxic-ischemic encephalopathy. Methods We performed a retrospective case-control study in 108 asphyxiated infants, admitted to nine tertiary departments for neonatal intensive care from January 2004 to July 2017, of whom 54 underwent hypothermia treatment and 54 did not. The concentrations of S100B protein in urine were measured using an immunoluminometric assay at first urination and 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120 h after birth. The results were correlated with the achievement of S100B levels within normal ranges at 72 h from hypothermia treatment. Routine laboratory parameters, longitudinal cerebral function monitoring, cerebral ultrasound and neurologic patterns were assessed according to standard protocols. Results Higher S100B concentrations were found in hypothermia-treated infants in both moderate (up to 12 h) and severe (up to 24 h) hypoxic-ischemic encephalopathy. S100B levels returned to normal ranges starting from 20 h of hypothermia treatment in moderate and from 36 h in severe hypoxic-ischemic encephalopathy. Conclusions The present results offer additional support to the usefulness of longitudinal neuro-biomarkers monitoring in asphyxiated infants treated by hypothermia. The pattern of S100B concentrations during hypothermia supports the need for further investigations aimed at reconsidering the time-window for patient recruitment and treatment, and the optimal duration of the cooling and rewarming phases of the hypothermia procedure.