Abstract
Purpose: Curcumin is known for its neuroprotective, anti-inflammatory and anti-oxidant properties and has been investigated as a potential therapeutic drug for Temporal Lobe Epilepsy (TLE). We previously found anti-epileptogenic properties of curcumin in an in vitro brain slice model for epileptogenesis, and inhibitory effects on the MAPK-pathway in vivo after intracerebrally applying curcumin in post-status epilepticus rats. Here, we investigated whether the intracerebral application of curcumin could be anti-epileptogenic in the rapid kindling rat model for TLE.
Methods: Curcumin or vehicle was injected directly into the brain through an intracerebral ventricular cannula at 5 consecutive days during the kindling process. Kindling consisted of repeated electrical stimulations of the angular bundle (12 times a day with a 30 min interval) every other day, until rats were fully kindled or until 36 stimulations were administered. One week after kindling acquisition, additional kindling stimulations were applied in a re-test in the absence of curcumin- or vehicle treatment.
Results: Curcumin-treated rats required more stimulations compared to vehicle-treated rats to reach Racine stage IV seizures, indicating that curcumin delayed seizure development. However, it did not prevent the fully kindled state as shown in the re-test. Increasing the dose of curcumin did not produce a delay in seizure development. Immunohistochemistry showed that kindling produced cell loss, astrogliosis, mossy fiber sprouting and neurogenesis in the dentate gyrus, which were not different between vehicle- and curcumin-treated groups.
Conclusion: Although curcumin’s effects on neuropathology were not detected and the delay of kindling development was transient, the data warrant further exploration of its anti-epileptogenic potential using formulations that further increase its bioavailability.
Methods: Curcumin or vehicle was injected directly into the brain through an intracerebral ventricular cannula at 5 consecutive days during the kindling process. Kindling consisted of repeated electrical stimulations of the angular bundle (12 times a day with a 30 min interval) every other day, until rats were fully kindled or until 36 stimulations were administered. One week after kindling acquisition, additional kindling stimulations were applied in a re-test in the absence of curcumin- or vehicle treatment.
Results: Curcumin-treated rats required more stimulations compared to vehicle-treated rats to reach Racine stage IV seizures, indicating that curcumin delayed seizure development. However, it did not prevent the fully kindled state as shown in the re-test. Increasing the dose of curcumin did not produce a delay in seizure development. Immunohistochemistry showed that kindling produced cell loss, astrogliosis, mossy fiber sprouting and neurogenesis in the dentate gyrus, which were not different between vehicle- and curcumin-treated groups.
Conclusion: Although curcumin’s effects on neuropathology were not detected and the delay of kindling development was transient, the data warrant further exploration of its anti-epileptogenic potential using formulations that further increase its bioavailability.
| Original language | English |
|---|---|
| Article number | 106873 |
| Number of pages | 8 |
| Journal | Epilepsy Research |
| Volume | 181 |
| DOIs | |
| Publication status | Published - 1 Mar 2022 |
Keywords
- Anti-inflammatory
- Epileptogenesis
- Intracerebral
- Natural compound
- Rat