Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Exp Neurol. 2009 Sep;219(1):126-35. doi: 10.1016/j.expneurol.2009.05.018. Epub 2009 May 19.

Antiepileptic effects of silk-polymer based adenosine release in kindled rats.

Author information

  • 1Robert S. Dow Neurobiology Laboratories, Legacy Research, 1225 NE 2nd Avenue, Portland, OR 97232, USA.

Abstract

Pharmacotherapy for epilepsy is limited by high incidence of pharmacoresistance and failure to prevent development and progression of epilepsy. Using the rat hippocampal kindling model, we report on the therapeutic potential of novel silk-based polymers engineered to release the anticonvulsant adenosine. Polymers were designed to release 1000 ng adenosine per day during a time span of ten days. In the first experiment rats were kindled by hippocampal electrical stimulation until all animals reacted with stage 5 seizures. Adenosine-releasing or control polymers were then implanted into the infrahippocampal fissure ipsilateral to the site of stimulation. Subsequently, only recipients of adenosine-releasing implants were completely protected from generalized seizures over a period of ten days corresponding to the duration of sustained adenosine release. To monitor seizure development in the presence of adenosine, adenosine-releasing or control polymers were implanted prior to kindling. After 30 stimulations--delivered from days 4 to 8 after implantation--control animals had developed convulsive stage 5 seizures, whereas recipients of adenosine-releasing implants were still protected from convulsive seizures. Kindling was resumed after nine days to allow expiration of adenosine release. During additional 30 stimulations, recipients of adenosine-releasing implants gradually resumed kindling development at seizure stages corresponding to those when kindling was initially suspended, while control rats resumed kindling development at convulsive seizure stages. Blockade of adenosine A1 receptors did not exacerbate seizures in protected animals. We conclude that silk-based adenosine delivery exerts potent anti-ictogenic effects, but might also have at least partial anti-epileptogenic effects. Thus, silk-based adenosine augmentation holds promise for the treatment of epilepsy.

Comment in

PMID:
19460372
[PubMed - indexed for MEDLINE]
PMCID:
PMC2728789
Free PMC Article

Images from this publication.See all images (5)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk