Current state of neuroprotective therapy using antibiotics in human traumatic brain injury and animal models.

TBI is a leading cause of death and disability in young people and older adults worldwide. There is no gold standard treatment for TBI besides surgical interventions and symptomatic relief. Post-injury infections, such as lower respiratory tract and surgical site infections or meningitis are frequent complications following TBI. Whether the use of preventive and/or symptomatic antibiotic therapy improves patient mortality and outcome is an ongoing matter of debate. In contrast, results from animal models of TBI suggest translational perspectives and support the hypothesis that antibiotics, independent of their anti-microbial activity, alleviate secondary injury and improve neurological outcomes. These beneficial effects were largely attributed to the inhibition of neuroinflammation and neuronal cell death. In this review, we briefly outline current treatment options, including antibiotic therapy, for patients with TBI. We then summarize the therapeutic effects of the most commonly tested antibiotics in TBI animal models, highlight studies identifying molecular targets of antibiotics, and discuss similarities and differences in their mechanistic modes of action.

Early postoperative neurocognitive complications in elderly patients: comparing those with and without preexisting mild cognitive impairment- a prospective study.

BACKGROUND: As societies age, increasing numbers of older adults undergo surgeries with anesthesia. Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) frequently occur in older surgical patients. Most of these patients already have preoperative mild cognitive impairment (MCI). However, the correlation between MCI and POD remains unclear. This study aimed to determine the incidence of POD in elderly patients with and without preexisting MCI. METHODS: A prospective study enrolled patients aged 60 years and above scheduled for major surgeries between December 2017 and April 2022. Preoperative MCI was determined by a Montreal Cognitive Assessment (MoCA) score between 18 and 24. POD was diagnosed using criteria from the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). POCD was characterized by a MoCA score reduction of 2 or more points from the preoperative score. The primary outcome was the incidence of POD within the first 72 h postoperatively. Secondary outcomes encompassed other postoperative complications, including POCD. RESULTS: The study comprised 223 elderly patients with MCI and 56 without MCI. The incidence of POD was 16.6% in the MCI group and 14.3% in the non-MCI group (P = 0.839). POCD occurred in 24.3% of MCI patients and 50% of non-MCI patients (P = 0.001). There were no significant differences in other postoperative complications between the groups. Postoperatively, the MCI group notably declined in visuospatial, attention, and orientation domains, while the non-MCI group declined in all domains except delayed recall. CONCLUSIONS: The incidence of POD was similar in the MCI and non-MCI groups. However, the non-MCI group demonstrated a higher incidence of POCD than the MCI group. This was identified by a reduction in postoperative MoCA scores for the visuospatial, naming, attention, language, abstraction, and orientation domains. These findings underscore the importance of postoperative cognitive assessments for both elderly patients with preexisting MCI and those with previously intact cognitive functions. TRIAL REGISTRATION: This trial was retrospectively registered in the Thai Clinical Trials Registry on 15/01/2019 (registration number: TCTR20190115001).

Sortilin is dispensable for secondary injury processes following traumatic brain injury in mice.

Traumatic brain injury (TBI) is characterized by complex secondary injury processes involving the p75 neurotrophin receptor (p75NTR), which has been proposed as a possible therapeutic target. However, the pathogenic role of the p75NTR co-receptor sortilin in TBI has not been investigated. In this study, we examined whether sortilin contributes to acute and early processes of secondary injury using a murine controlled cortical impact (CCI) model of TBI. Initial expression analysis showed a down-regulation of sortilin mRNA levels 1 and 5 day post injury (dpi) and a reduced expression of sortilin protein 1 dpi. Next, a total of 40 SortilinΔExon14 loss-of-function mouse mutants (Sort1-/-) and wild-type (Sort1+/+) littermate mice were subjected to CCI and examined at 1 and 5 dpi. Neither sensorimotor deficits or brain lesion size nor CCI-induced cell death or calcium-dependent excitotoxicity as evaluated by TUNEL staining or Western blot analysis of alpha II spectrin breakdown products were different between Sort1-/- and Sort1+/+ mice. In addition, CCI induced the up-regulation of pro-inflammatory marker mRNA expression (Il6, Tnfa, Aif1, and Gfap) irrespectively of the genotype. Similarly, the mRNA expressions of neurotrophins (Bdnf, Ngf, Nt3), VPS10P domain receptors others than sortilin (Ngfr, Sorl1, Sorcs2), and the sortilin interactor progranulin were not affected by genotype. Our results suggest that sortilin is a modulatory rather than a critical factor in the acute and early brain tissue response after TBI.