Abstracts

RATIONALE: Photodynamic therapy (PDT) has been used in treatment of some forms of cancer, to target abnormal tissue with a photoactive dye that is preferentially taken up by tumor cells. PDT combines the uptake of a photosensitizing agent with exposure to laser light; the consequent excitation of the photosensitizing compounds causes the release of singlet oxygen (a free radical) that results in cytotoxicity. Cells that preferentially take up the dye are killed, with limited damage to the surrounding normal tissue. Application of this treatment for epilepsy may allow clinicians to selectively label and kill cells involved in seizure generation, leaving normally-functioning brain unharmed. The objective of the current study was to determine the safety of PDT in a rat model of epilepsy. Specifically, we examined performance on a behavior that is thought to depend on intact hippocampal function, following injection of photosensitizing dye and laser exposure in kindled rats.
METHODS: The study was composed of 4 groups of 8 animals each. Group A was a na[iuml]ve control, Group B received a unilateral craniectomy and sham laser application. Groups C and D were implanted with bipolar stimulating electrodes in the perforant path, and were subsequently kindled (3 consecutive stage 5 seizures). Animals in this group received injections of 5-aminoluvelinic acid (ALA), an FDA-approved photosensitizing agent, followed by one induced generalized seizure on the day of laser treatment. Group C, in addition, received a unilateral craniectomy and sham laser application, while Group D received a unilateral craniectomy followed by 10 minutes of laser treatment (laser wavelength of 635 nanometers; laser positioned 2.3 centimeters from the surface of the brain). After a 1 week recovery period, all animals underwent a behavioral battery which included the Morris Water Maze (MWM) (dependent on intact hippocampal function) and an inclined plane evaluation.
RESULTS: Statistical analysis of performance on the MWM task indicated that there were no significant differences between animals that received laser treatment and control animals [F=.920, (df=3,27), p=.445, between groups]. In addition, there were no differences across groups on the inclined plane assessment.
CONCLUSIONS: Preliminary data suggests that unilateral PDT in this model of epilepsy does not impair hippocampal mediated spatial learning as measured by the MWM. Further, this therapeutic modality does not cause significant motor weakness as determined by the incline plane test. Conclusions regarding PDT safety await further behavioral (and histological) analysis.
[Supported by: C.U.R.E.
Bronte Foundation]