Effect of lidocaine on cognitively impaired rats: Anti‐inflammatory and antioxidant mechanisms in combination with CRMP2 antiphosphorylation

OBJECTIVE: Studies have shown that lidocaine has antioxidative stress, anti‐inflammatory, and nerve‐protective effects. The current study investigated the effects of lidocaine on cognitive function in rats with cognitive dysfunction. METHODS: A total of 48 rats were randomly assigned to four groups of 12 rats each: control group; L (lidocaine) + D (d‐galactose) group, d‐galactose group (D group); and D + L group. We assessed cognitive function using a Morris water maze (MWM) and pathologic changes of hippocampal sections. An enzyme‐linked immunosorbent assay (ELIZA) was used to detect serum malondialdehyde (MDA) and superoxide dismutase (SOD) levels in rats, and protein immunoblotting (western blot) was used to detect brain tissue proteins (collapsing response mediator protein‐2 [CRMP2], phosphorylated‐collapsing response mediator protein‐2 [P‐CRMP2], and β‐amyloid protein [Aβ]). RESULTS: The MWM showed that the d‐gal group (284.09 ± 20.46, 5.20 ± 0.793) performed worse than the L + D (265.37 ± 22.34, 4.170 ± 0.577; p = .000) and D + L groups (254.72 ± 27.87, 3.750; p = .000) in escape latency and number of platform crossings, respectively. The L + D group (44.94 ± 2.92 pg/mL, 6.22 ± 0.50 pg/mL, and 460.02 ± 8.26 nmol/mL) and D + L group (46.88 ± 2.63 pg/mL, 5.90 ± 0.38 pg/mL, and 465.6 ± 16.07 nmol/mL) had significantly lower serum inflammatory levels of interleukin‐6, tumor necrosis factor‐α, and MDA than the d‐gal group (57.79 ± 3.96 pg/mL, 11.25 ± 1.70 pg/mL, and 564.9 ± 15.90 nmol/mL), respectively. The L + D group (3.17 ± 0.41 μg/mL) and D + L group (3.08 ± 0.09 μg/mL) had significantly higher serum inflammatory levels of SOD than the d‐gal group (2.20 ± 0.13 μg/mL) (all p = .000). The levels of CRMP2, P‐CRMP2, and Aβ in the brain tissue homogenates of the L + D group (0.87 ± 0.04, 0.57 ± 0.0, and 0.16 ± 0.02) and the D + L group (0.82 ± 0.05, 0.58 ± 0.09, and 0.15 ± 0.02) were significantly different than the d‐gal group (0.67 ± 0.03, 0.96 ± 0.040, and 0.29 ± 0.05). CONCLUSIONS: Lidocaine was shown to reduce cognitive impairment in rats with cognitive dysfunction through anti‐inflammatory and antioxidative stress mechanisms in combination with CRMP2 antiphosphorylation.