Pharmacodynamic Effects of Standard versus High Caffeine Doses in the Developing Brain of Neonatal Rats Exposed to Intermittent Hypoxia

(1) Background: Caffeine citrate, at standard doses, is effective for reducing the incidence of apnea of prematurity (AOP) and may confer neuroprotection and decrease neonatal morbidities in extremely low gestational age neonates (ELGANs) requiring oxygen therapy. We tested the hypothesis that high-dose caffeine (HiC) has no adverse effects on the neonatal brain. (2) Methods: Newborn rat pups were randomized to room air (RA), hyperoxia (Hx) or neonatal intermittent hypoxia (IH), from birth (P0) to P14 during which they received intraperitoneal injections of LoC (20 mg/kg on P0; 5 mg/kg/day on P1-P14), HiC (80 mg/kg; 20 mg/kg), or equivalent volume saline. Blood gases, histopathology, myelin and neuronal integrity, and adenosine receptor reactivity were assessed. (3) Results: Caffeine treatment in Hx influenced blood gases more than treatment in neonatal IH. Exposure to neonatal IH resulted in hemorrhage and higher brain width, particularly in layer 2 of the cerebral cortex. Both caffeine doses increased brain width in RA, but layer 2 was increased only with HiC. HiC decreased oxidative stress more effectively than LoC, and both doses reduced apoptosis biomarkers. In RA, both caffeine doses improved myelination, but the effect was abolished in Hx and neonatal IH. Similarly, both doses inhibited adenosine 1A receptor in all oxygen environments, but adenosine 2A receptor was inhibited only in RA and Hx. (4) Conclusions: Caffeine, even at high doses, when administered in normoxia, can confer neuroprotection, evidenced by reductions in oxidative stress, hypermyelination, and increased Golgi bodies. However, varying oxygen environments, such as Hx or neonatal IH, may alter and modify pharmacodynamic actions of caffeine and may even override the benefits caffeine.

Four Quadrant Osteoplastic Decompressive Craniotomy versus Conventional Decompressive Craniectomy for Traumatic Brain Injury: A Randomized Controlled Trial

Objective Four quadrant osteoplastic decompressive craniotomy (FoQOsD) has been described as a novel technique in the management of patients with traumatic brain injury requiring decompressive surgery. There has not been a randomized controlled trial comparing its outcomes with conventional decompressive craniectomy (DECRA) as yet. Methods A randomized controlled trial of 55 patients was conducted, of whom 29 underwent DECRA and 26 patients underwent FoQOsD. The preoperative baseline demographics, clinical conditions, and radiologic features were similar in both the groups. Clinical outcome was decided by the use of Glasgow coma outcome scale extended (GOS-e) at 3 months. Radiographic outcomes were assessed by measurement of the change in midline shift and brain width expansion (ipsilateral and contra-lateral to hematoma) on the postoperative computed tomographic (CT) scan. Results No significant differences were identified in baseline demographics, clinical condition, Rotterdam CT score, and radiographic characteristics between both the groups. At 3-month follow-up, the mean GOS-e score was comparable in both the groups (3.23 in DECRA group and 3.35 in FoQOsD group, p = 0.856). Mortality analysis at 3 months revealed that nine patients died in the DECRA group and eight died in FoQOsD group. Postoperative imaging characteristics, including Rotterdam score, also did not differ significantly. The percentage reduction in midline shift and percentage brain width expansion on the postoperative CT scan was similar in both the groups (p > 0.05). Conclusion FoQOsD appears to be at least as efficacious as DECRA in providing equivalent clinical outcomes with the added benefit of avoiding a second surgery.