Backgrounds: Traumatic brain injury has high mortality and morbidity. The involvement of neuroinflammatory responses and neuronal damage in traumatic brain injury is the basis for the development of renewable neuroprotective agents, one of which is the amino acid L-Arginine. The amino acid L-Arginine which can be found in Giant Snake Head fish (Channa micropeltes) is thought to inhibit anti-inflammatory effects through the Arg-1 signaling pathway. Aims: To prove and analyze the effect of giving L-Arginine Giant Snake Head fish on neuroinflammation and neuronal damage in a rat model of traumatic brain injury. Methods: This randomized controlled trial (RCT) study used a posttest-only control group design. Thirty-five male rats (Rattus norvegicus) with the Wistar strain were randomly divided into five treatment groups, namely the normal control group (N), negative control (KN), and 3 treatment groups (A-C). The KN and A-C groups were modeled after traumatic brain injury and given L-Arginine at a dose of 0.5; 1.5; and 3 g/kgBW/day for 7 days specifically A-C. Brain tissue samples were used for the examination of TLR4, TNF-α, GSDMD, Caspase-3, and histopathological features. All data were analyzed using the Kruskall-Wallis test, except for GSDMD expression with a significance <0.05. Results: The mean TLR4 expression in A (15.7 ± 5.35), B (12.9 ± 5.67), and C (11.4 ± 6.27) were lower and significant compared to KN, but higher and significant compared to N. The same pattern appears in the decrease in TNF-α expression, Caspase-3 expression, and histopathology of brain tissue damage. The mean relative expression of GSDMD to N in A (1.3 ± 0.53), B (1.2 ± 0.52), and C (1.2 ± 0.60) was higher than in KN, but not significant. Relative expression of GSDMD to Beta Actin, A and B have the same higher expression than C, KN, and N. Conclusion: Expression of TLR-4, TNF-α, Caspase-3 and histopathology of brain tissue damage in traumatic brain injury model rats given Giant Snake Head fish L-Arginine were lower than without L-Arginine. Meanwhile, the expression of GSDMD in traumatic brain injury model rats when given Giant Snake Head fish L-Arginine was slightly higher than without L-Arginine.
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