Curcumin Lowers the Accelerated Speed of Epileptogenesis by Traumatic Brain Injury.

Background: Traumatic brain injury or TBI can underlie epilepsy. Prevention of PTE has been of great interest to scientists. Given the antiepileptic, antioxidant and anti-inflammatory activities of curcumin, we examined whether this compound can affect epileptogenesis in rats after TBI. Methods: Curcumin was injected once a day for two weeks. TBI was induced in the temporal cortex of anesthetized rats using a controlled cortical impact device. One day after TBI, pentylenetetrazole (PTZ), 35 mg/kg, was injected i.p. every other day until manifestation of generalized seizures. The number of PTZ injections was then recorded. Moreover, the extent of cortical and hippocampal IL-1ß and glial fibrillary acidic protein (GFAP) expression in the epileptic rats were measured by Western blot analysis. Results: Curcumin 50 and 150 mg/kg prevented the development of kindling, whereas TBI accelerated the rate of kindling. Curcumin 20 mg/kg prohibited kindling facilitation by TBI, and reduced the expression of IL-1ß and GFAP induced by TBI. Conclusion: Curcumin can stop the acceleration of epileptogenesis after TBI in rats. Inhibiting hippocampal and cortical overexpression of IL-1ß and GFAP seems to be involved in this activity.

The effect of Lipopolysaccharide (LPS) pretreatment on hippocampal apoptosis in traumatic rats.

Objectives: Traumatic brain injury (TBI) is a serious medical problem that affects the quality of life. Apoptosis is a form of programmed cell death that happens after trauma. Effector caspases are responsible for initiating apoptosis.Methods: In the present study, we examined the effect of LPS preconditioning (0.1 and 0.5 mg/kg, ip; 5 days prior controlled cortical injury) on apoptosis, 4 and 12 hours after trauma. We investigated possible mechanisms on the expression of caspase3 and caspase7 in hippocampal CA1 and CA3 areas by using immunohistochemistry and Western blotting techniques and also TUNEL-positive cells.Results: Higher expression of caspase3 and caspase7 were accompanied by a higher number of dead neurons in traumatic rats 4 and 12 hours after trauma(P < 0.05). LPS preconditioning decreased caspase3 and caspase7over-expression and the number of dead neurons in the hippocampus(P < 0.05).Discussion: Our data indicate that LPS preconditioning inhibits neural damage and apoptosis induced by trauma in the hippocampus.

Traumatic brain injury accelerates kindling epileptogenesis in rats.

OBJECTIVES: Traumatic brain injury (TBI) is a well-known cause of symptomatic epilepsy. In animal models of post-traumatic epilepsy (PTE), progression of trauma to epilepsy takes several weeks to months. Although this long process is similar to clinical PTE, it is costly and laborious. We used a combination of TBI and kindling as an accelerated animal model to develop epilepsy in much shorter period compared to that occurring in PTE. METHODS: Traumatic brain injury was exerted to parieto-temporal cortex of anaesthetised rats by controlled cortical impact (CCI, 5 mm round tip, 4.5 mm/seconds velocity and 150 ms duration). Chemical kindling started 24 hours after CCI by intraperitoneal injection of 30 mg/kg pentylenetetrazole (PTZ) every other day until manifestation of three consecutive generalised seizures. Rapid electrical kindling of the amygdala began 1 week after TBI by exertion of 12 daily threshold stimuli (50 Hz mono-phasic square-wave stimulus of 1 ms per wave for 3 seconds) with 5 minutes interval between each stimulation until the rats became kindled. RESULTS: Controlled cortical impact injury accelerated rate of both chemical and electrical kindling. Number of PTZ injections required for acquisition of generalised seizures decreased from 13.1 ± 1.6 in sham-operated animals to 7.1 ± 0.3 in traumatic rats (p < 0.05). The required number of stimuli to elicit electrically kindled focal and generalised seizures decreased from 24.0 ± 3.9 and 80 ± 6.5 in sham-operated animals to 6.6 ± 0.9 and 53 ± 6.5 in traumatic rats (p < 0.01), respectively. LIMITATIONS: Unlike the animal models of PTE in which recurrent seizures occur spontaneously after TBI, in our study, epilepsy is elicited by kindling stimulations. DISCUSSION: Traumatic brain injury facilitates acquisition of epilepsy in both chemical and electrical kindling models. Combination of trauma and kindling can be considered as an inexpensive and time-saving animal model in PTE studies.

Lipopolysaccharide preconditioning prevents acceleration of kindling epileptogenesis induced by traumatic brain injury.

10-20% of symptomatic epilepsies are post-traumatic. We examined effect of LPS preconditioning on epileptogenesis after controlled cortical impact (CCI). LPS (0.01, 0.1 and 0.5 mg/kg) was injected i.p. to rats 5 days before induction of CCI to parieto-temporal cortex. Kindling started 24h after CCI by i.p. injection of 30 mg/kg of pentylenetetrazole every other day until manifestation of 3 consecutive generalized seizures. CCI injury accelerated the rate of kindled seizures acquisition. LPS (0.1 and 0.5 mg/kg) prevented the acceleration of kindling. LPS preconditioning significantly decreased IL-1ß and TNF-α over-expression and the number of damaged neurons in the hippocampus of traumatic rats.