[PMC free article] [PubMed] [Google Scholar] 104

[PMC free article] [PubMed] [Google Scholar] 104. of the blood-brain barrier, or the common systemic distribution of their respective receptors. Consequently, in recent years a new field of cell and gene-based neuropharmacology offers emerged, aimed at either delivering endogenous anticonvulsant compounds by focal intracerebral transplantation of bioengineered cells (gene therapy), or by inducing epileptogenic mind areas to produce these compounds (gene therapy). With this review, recent efforts to develop GABA-, adenosine-, CSF2RB galanin-, and neuropeptide Y- centered cell and gene treatments are discussed. The neurochemical rationales for using these compounds are discussed, the advantages of focal applications are highlighted and preclinical cell transplantation and gene therapy studies are critically evaluated. Although many encouraging data have been generated recently, potential problems, such as long-term therapeutic effectiveness, long-term safety, and effectiveness in clinically relevant animal models, need to be tackled before medical applications can be contemplated. gene therapy), or the manifestation of antiepileptic providers can be directed to an epileptogenic region using gene delivery by viral vectors (gene therapy). CELL Treatments FOR EPILEPSY – RATIONALE Temporal lobe epilepsy, probably one of the most common forms of focal, or partial, epilepsy is also probably one of the most hard forms of epilepsy to treat since seizure activity often progresses from focal to secondarily generalized, C and frequently pharmacoresistant C seizures. Thus, restorative alternatives are urgently needed and several focal treatment methods Erlotinib for refractory epilepsy have been tested. These experiments shown that focal drug delivery is generally well tolerated and devoid of major side effects [119]. Focal drug delivery can be achieved by devices such as synthetic slow-release polymers, pump systems, which can be coupled to integrated seizure prediction systems [153], or by cellular implants. Strategies that were adopted focused either within the cell-mediated paracrine launch of antiepileptic compounds, the alternative of lost neurons, the practical integration of cellular implants into preexisting neuronal networks, or various mixtures thereof. One method of packaging and implanting cell-loaded products into the CNS of recipients is definitely by encapsulating cell suspensions inside a polymer membrane prior to implantation [38]. Cells/cells packaged within an encapsulating membrane obviate the need for immunosuppressive therapies in transplant recipients. In addition, the device output can be quantified prior to implantation, and following a removal of the implant. It has been shown that encapsulated cells can survive for at least a yr in graft recipients [169]. The ability to retrieve the devices with the presently used tubular configurations also confers an additional margin of security over non-encapsulated cell implants. Encapsulated cell grafting is currently being developed for a wide range of applications including chronic pain control [170] and has already proceeded into medical trials almost 10 years ago [1, 2]. However, the long-term survival of encapsulated cell grafts C a requirement for epilepsy individuals, who are expected to live for decades after treatment C is still a major challenge requiring the design of improved biomaterials and coordinating cells. In contrast, the direct transplantation and practical integration of restorative cells into the mind may offer the perspective for long-term survival of the graft. However, for the design of direct cell therapies inflammatory and immunolo-gical reactions of the brain have to be regarded as: While lipopolysaccharide-induced mind swelling strongly impaired basal Erlotinib hippocampal neurogenesis in rats Erlotinib [36], more recent data suggest that long-term impairment of dentate neurogenesis, as reported previously after kainic acid-induced status epilepticus, is definitely not a general feature of chronic epilepsy [16]. Therefore, a substantial proportion of adult granule cells found six months after status epilepticus were created during the 1st two weeks after the insult despite chronic swelling [16]. These findings imply that inflammatory responses of the epileptic hippocampus are not likely to compromise the effectiveness of cellular implants. On the other hand the brain is not as immunologically privileged as pre-viously thought and immunological relationships have to be regarded as, when designing cell transplantation studies [7]. Despite these potential hurdles, medical cell transplantation tests.