Table 2 Summarized findings of the impact of various pharmacotherapies on TBI-induced gut inflammation
Therapy | Intervention | Sex | Species | Model | Timepoints | Impact on gut inflammation |
|---|---|---|---|---|---|---|
Serotonin | SSRIs (IP fluoxetine) 5 mg/kg, single dose immediately after injury | N/A | Mice | Single unilateral, severe TBI (CCI) | 4 days post-TBI | Preserves colonic barrier integrity by reducing FITC-dextran permeability [117] |
Ghrelin | 2 doses of IP ghrelin (20 μg total), one hour before and right after TBI | Male | Mice | Single unilateral, severe TBI (WD) | 6 h post-TBI | Maintains ileal barrier integrity and architecture and decreases TNF-α levels [171] |
1 dose of IV ghrelin (20 μg/kg) 30 min after TBI | Male | Rats | Single unilateral severe TBI (CCI) | 1–3 days post-TBI | Improves intestinal motility and protects ileum mucosal epithelium [175] | |
2 doses of IP ghrelin (20 μg total) right after ICH | Male | Mice | Intracerebral hemorrhage (ICH) | 1 day post ICH | Reduces ileal permeability by upregulating tight junctions ZO-1 and claudin-5 [176] | |
Progesterone | SQ progesterone (16 mg/kg) daily for 5 days post-TBI | Male | Rats | Single unilateral TBI (WD) | 5 days post-TBI | Downregulates the expressions of ileum TNF-α, IL-1β, and ICAM1 and reduces mucosal apoptosis [203] |
SQ progesterone (16 mg/kg) daily for 5 days post-TBI | Male | Rats | Single unilateral TBI (WD) | 5 days post-TBI | Reduces ileum NF-κB activation and proinflammatory cytokines expression [204] | |
IP progesterone (16 mg/kg) daily for 5 days post-SAH | Male | Rats | Subarachnoid hemorrhage (SAH) | 5 days post-SAH | Restores ileum mucosal integrity and reduces proinflammatory cytokines IL-1β, TNF-α and IL-6 [208] | |
Beta-blockers | 1 dose of IP labetalol (30 mg/kg) right after TBI | Male | Rats | Single unilateral TBI (WD) | 3, 6, and 12 h post-TBI | Decreases hyperactivity of adrenergic tone, reduces intestinal TNF-α levels, and prevents an increase in ileum permeability [227] |
PO labetalol (62.5 μM in 1 M sucrose) after TBI | Male and Female | Drosophila | Closed head TBI using high-impact trauma device | 24 h post-TBI | Reduces intestinal permeability and early mortality [221] | |
Statins | One dose of IP rosuvastatin (30 mg/kg) right after TBI | Male | Rats | Single unilateral TBI (WD) | 24 h post-TBI | Downregulates jejunal TNF-α and IL-1β levels and enhances villous histology by blocking the CD40/NF-κB pathway [261] |
PO atorvastatin (10 mg/kg) daily 3 days before inducing ischemia | Male | Rats | Intestinal ischemia reperfusion injury (IRI) | 3 h post-reperfusion | Promotes ileum motility possibly through reducing oxidative stress and increasing glutathione levels [264] | |
Antibiotics/probiotics | PO ampicillin, metronidazole, vancomycin, neomycin (1g/L) daily for 2 weeks pre-TBI | Male | Mice | Single unilateral TBI (CCI) | 3 days post-TBI | Improves intestinal permeability by increasing epithelial ZO1 expression in the cecum [269] |
PO gavage lactobacillus acidophilus (1 × 1010 CFU) one daily until sacrificed | Male | Mice | Single unilateral TBI (WD) | 1,3 and 7 days post-TBI | Reduces ileum inflammation, maintains barrier integrity, and promotes gut motility through PKC/MLCK/MLC signaling pathway [276] | |
PO gavage lactobacillus acidophilus (1 × 1010 CFU) one daily until sacrificed | Male | Mice | Single unilateral TBI (WD) | 1,3 and 7 days post-TBI | Improves ileum barrier function and gut’s absorptive capacity for nutrients and electrolytes [275] |