AT2 activation does not influence brain damage in the early phase after experimental traumatic brain injury in male mice.

Antagonism of the angiotensin II type 1 receptor (AT1) improves neurological function and reduces brain damage after experimental traumatic brain injury (TBI), which may be partly a result of enhanced indirect angiotensin II type 2 receptor (AT2) stimulation. AT2 stimulation was demonstrated to be neuroprotective via anti-inflammatory, vasodilatory, and neuroregenerative mechanisms in experimental cerebral pathology models. We recently demonstrated an upregulation of AT2 after TBI suggesting a protective mechanism. The present study investigated the effect of post-traumatic (5 days after TBI) AT2 activation via high and low doses of a selective AT2 agonist, compound 21 (C21), compared to vehicle-treated controls. No differences in the extent of the TBI-induced lesions were found between both doses of C21 and the controls. We then tested AT2-knockdown animals for secondary brain damage after experimental TBI. Lesion volume and neurological outcomes in AT2-deficient mice were similar to those in wild-type control mice at both 24 h and 5 days post-trauma. Thus, in contrast to AT1 antagonism, AT2 modulation does not influence the initial pathophysiological mechanisms of TBI in the first 5 days after the insult, indicating that AT2 plays only a minor role in the early phase following trauma-induced brain damage.

Deep neuromuscular blockade for endolaryngeal procedures: A multicenter randomized study.

OBJECTIVES/HYPOTHESIS: The aim of the present study was to compare the surgical condition between deep neuromuscular blockade (NMB) and moderate NMB. STUDY DESIGN: Multicenter, randomized, parallel intervention trial. METHODS: One hundred two patients underwent microscopic endolaryngeal surgery at four university hospitals. The patients were randomized into moderate NMB (train-of-four 1-2) (M group) or deep NMB (post-tetanic count 1-2) (D group) with moderate or high doses of rocuronium, respectively. Surgical rating conditions (SRCs) were evaluated during the surgery. Sugammadex was given to the M group at 2 mg/kg and the D group at 4 mg/kg. Perioperative clinical signs and conditions were recorded until discharge from the postanesthesia care unit. RESULTS: Clinically acceptable SRC was observed in 49 patients (100%) in the D group and 43 patients (89.6%) in the M group (P = .027). The frequency of notable vocal fold movement in the M group was significantly higher than the D group (70.8% vs. 32.7%). The patients in the M group required more additional doses of rocuronium (47.9%) than the D group (20.4%) to maintain full relaxation (P = .005). The median time (interquartile range) from administration of sugammadex to train-of-four ratio 0.9 in the D group was shorter than the M group (120 [109-180 minutes] vs. 180 minutes [120-240 minutes], P = .034). CONCLUSIONS: Deep NMB with high doses of rocuronium combined with 4 mg/kg of sugammadex for reversal during endolaryngeal surgery provided better SRC and anesthetic conditions than moderate NMB of rocuronium with 2 mg/kg of sugammadex. LEVEL OF EVIDENCE: 1b Laryngoscope, 130:437-441, 2020.

The antioxidative, non-psychoactive tricyclic phenothiazine reduces brain damage after experimental traumatic brain injury in mice.

Oxidative stress due to free radical formation is an important mechanism of secondary brain damage following traumatic brain injury (TBI). Phenothiazine has been found to be a strong antioxidant in eukaryotic cells in vitro and in invertebrates in vivo. The present study was designed to determine the neuroprotective potency of unsubstituted phenothiazine in a paradigm of acute brain injury. Thirty minutes after pneumatic, controlled cortical impact (CCI) injury, C57BI6 mice were randomly assigned to "low dose" (3 mg/kg, LD) or "high dose" (30 mg/kg, HD) s.c. phenothiazine or vehicle treatment. Brain lesion, neurofunctional impairment, body weight, and markers of cerebral inflammation were determined 24h after the insult. Phenothiazine treatment dose-dependently reduced brain lesion volume (LD: -19.8%; HD: -26.1%) and posttraumatic body weight loss. There were no significant differences in the neurological function score and in markers of cerebral inflammation (Iba-1 positive cells, TNFα expression), whereas iNOS expression was significantly lower compared to vehicle-treated animals. Phenothiazine appears to modify in a post-treatment protocol certain aspects of secondary brain damage in vivo at unusually low concentrations, in particular the cortical contusion volume after TBI. The potential role of the reduced iNOS expression is unclear at present.