There are various treatment modalities for chronic subdural hematoma (CSDH) and there is extensive debate surrounding pharmaceutical interventions. There is no consensus regarding the relative efficacy and safety of multiple treatment modalities. This study aims to investigate this issue and offer potential clinical recommendations.

We searched PubMed, Web of Science, Embase and the Cochrane Library from January 2000 to May 2023 to identify randomized and nonrandomized controlled studies reporting one or more outcomes associated with the pharmacologic management of CSDH. The primary outcomes of interest included recurrence, favorable prognosis and adverse events, while the secondary outcomes included a reduction in hematoma volume and mortality. Pooled estimates, credible intervals and odds ratios were calculated for all outcomes using a fixed effects model. Confidence in network meta-analysis judgments were employed to stratify the evidential quality. This study was registered with PROSPERO: CRD42023406599.

The search strategy yielded 656 references; ultimately, 36 studies involving 8082 patients fulfilled our predefined inclusion criteria. The findings suggested that statins + glucocorticoids (GCs) ranked highest for preventing recurrence, improving prognosis and facilitating hematoma absorption. Tranexamic acid ranked second highest for preventing recurrence. Statins were found to be the preferred drug intervention for decreasing mortality and preventing adverse events. Antithrombotic agents ranked lowest in terms of decreasing mortality and improving prognosis.

Our findings indicate that statins + GCs may be the most effective treatment modality for preventing recurrence, improving patient prognosis and facilitating hematoma absorption. In terms of reducing mortality and preventing adverse events, statins may be superior to other pharmacological interventions. Routine use of GCs is not suggested for patients with CSDH. Further prospective research is needed to directly compare the efficacy and superiority of various pharmaceutical interventions targeting CSDH to reinforce and validate our findings.

Traumatic brain injury (TBI) can cause neuroinflammation and neuronal death. The role of mitochondrial dysfunction in regulating inflammasome activation during TBI remains unclear. This study aims to explore mitochondrial regulation of neuroinflammation and pyroptosis after TBI.

We used a mouse TBI model and in vitro scratch-injured HT22 cells and primary neurons to examine changes in mitochondrial dynamics and nucleotide-binding oligomerization domain-like receptors family pyrin domain-containing 3 (NLRP3) inflammasome activation. Metformin treatment, mitofusin 1 (Mfn1) knockdown and regulation of the Mfn1 pathway were applied to evaluate the therapeutic effects and mechanisms.

TBI triggered NLRP3 inflammasome activation and neuronal pyroptosis, along with impaired mitochondrial function and oxidative stress. Metformin reduced inflammasome activation, improved mitochondrial homeostasis, and alleviated neuronal injury. These effects were lost when Mfn1 was silenced, highlighting its essential role. Furthermore, we determined that the AMPK pathway modulates these observed effects.

Metformin protects against TBI-induced neuronal damage by restoring Mfn1-dependent mitochondrial dynamics and suppressing inflammasome activation. Mfn1 is a key mediator linking mitochondrial health to neuroinflammatory responses in TBI.