Brain edema and swelling is a critical factor in the high mortality and morbidity associated with traumatic brain injury (TBI). Despite this, the mechanisms associated with its development are poorly understood and interventions have not changed in over 30 years. Although neuropeptides and neurogenic inflammation have been implicated in peripheral edema formation, their role in the development of central nervous system edema after brain trauma has not been investigated. This study examines the role of the neuropeptide, substance P (SP), in the development of edema and functional deficits after brain trauma in rats. After severe diffuse TBI in adult male rats, neuronal and perivascular SP immunoreactivity were increased markedly. Perivascular SP colocalized with exogenously administered Evans blue, supporting a role for SP in vascular permeability. Inhibition of SP action by administration of the neurokinin-1 (NK1) antagonist, N-acetyl-L-tryptophan, at 30 mins after trauma attenuated vascular permeability and edema formation. Administration of the NK1 antagonist also improved both motor and cognitive neurologic outcomes. These findings suggest that SP release is integrally linked to the increased vascular permeability and edema formation after brain trauma, and that treatment with an NK1 receptor antagonist reduces edema and improves neurologic outcome.

Summary: Traumatic brain injury (TBI) remains one of the leading causes of mortality and morbidity worldwide in individuals under the age of 45 years, and, despite extensive efforts to develop neuroprotective therapies, there has been no successful outcome in any trial of neuroprotection to date. In addition to recognizing that many TBI clinical trials have not been optimally designed to detect potential efficacy, the failures can be attributed largely to the fact that most of the therapies investigated have been targeted toward an individual injury factor. The contemporary view of TBI is that of a very heterogenous type of injury, one that varies widely in etiology, clinical presentation, severity, and pathophysiology. The mechanisms involved in neuronal cell death after TBI involve an interaction of acute and delayed anatomic, molecular, biochemical, and physiological events that are both complex and multifaceted. Accordingly, neuropharmacotherapies need to be targeted at the multiple injury factors that contribute to the secondary injury cascade, and, in so doing, maximize the likelihood of a successful outcome. This review focuses on a number of such multifunctional compounds that have shown considerable success in experimental studies and that show maximum promise for success in clinical trials.

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Background: The usefulness of administrating adjunctive systemic antibiotics to expedite healing of periodontal tissues is a topic of interest given the lack of clear guidelines. Aim: To compare clinical outcomes in patients given adjunctive azithromycin (AZ), adjunctive amoxicillin plus metronidazole (AMX + MTZ), or scaling and root planing (SRP) alone in the treatment of moderate-to-severe chronic periodontitis. Methods: Thirty-eight patients were randomly assigned into: SRP alone; 500 mg AMX plus 400 mg MTZ three times per day for 7 days; or 500 mg AZ for 3 days. Antibiotics were administered after the first SRP session and clinical parameters for full-mouth and baseline probing pocket depth (PPD) categories were reviewed 2-months post-treatment. Results: Thirty-four of 38 patients completed the study. All groups experienced significant improvements in full-mouth clinical attachment level (CAL), probing pocket depth (PPD) and bleeding on probing. AZ exhibited greater reductions in PPD than SRP alone for baseline severe sites, whilst AMX+MTZ showed significant improvements in PPD and CAL than SRP alone for baseline moderate and severe sites. Of the two antibiotic therapies, AMX+MTZ showed greater reductions in PPD compared with AZ in baseline moderate sites only. Conclusions: For patients with moderate-to-severe periodontitis, adjunctive systemic antibiotics might result in greater clinical benefits.Keywords: Amoxicillin, azithromycin, chronic periodontitis, metronidazole, scaling and root planing.Abbreviations and acronyms: AMX + MTZ = amoxicillin plus metronidazole; AMX = amoxicillin; AZ = azithromycin; BOP = bleeding on probing; CAL = clinical attachment level; MTZ = metronidazole; PPD = probing pocket depth; RCT = randomized controlled trial; SRP = scaling and root planning; TID = three times per day.