Permeating the Blood Brain Barrier and Abrogating the Inflammation in Stroke: Implications for Stroke Therapy

Bentham Science Publishers



Current Pharmaceutical Design, 2012, 18, 3670-3676

Cesar V. Borlonganb,*, Loren E. Gloverb, P.R. Sanbergb and David C. Hessa,*



Cell therapy has been shown as a potential treatment for stroke and other neurological disorders. Human umbilical cord blood (HUCB) may be a promising source of stem cells for cell therapy. The most desired outcomes occur when stem cells cross the blood brain barrier (BBB) and eventually reach the injured brain site. We propose, from our previous studies, that mannitol is capable of dis- rupting the BBB, allowing the transplanted cells to enter the brain from the periphery. However, when the BBB is compromised, the in- flammatory response from circulation may also be able to penetrate the brain and thus may actually exacerbate the stroke rather than af- ford therapeutic effects. We discuss how an NF-kB decoy can inhibit the inflammatory responses in the stroke brain thereby reducing the negative effects associated with BBB disruption. In this review, we propose the combination of mannitol-induced BBB permeation and NF-kB decoy for enhancing the therapeutic benefits of cell therapy in stroke.



Cell therapies are a revolutionary treatment for neurodegenera- tive diseases. Similar to traditional drug therapies, experimentation must determine many factors for the safety and efficacy of stem cell treatments such as the correct dose, delivery route, and optimal time of intervention [50]. Stem cell lines must be validated through mul- tiple laboratories with different animal models before clinical trials can be authorized [50]. This year, the National Institute of Health is studying the safety and efficacy of stem cells used as treatment for stroke in clinical trials at various stages of recruitment and comple- tion [51]. Eight stem cell products are being evaluated in these trials [50]. Laboratory experimentation is crucial to confirm the mecha- nisms by which particular stem cells, like HUCB cells, provide their neuroprotective as well as neuroregenerative effects in stroke treatment [52-56]. The key to maintaining parallel and thus confir- matory experimentation requires the use of standard protocols for stem cell therapies. The experimental design paradigms created by Stroke Therapy Academic Industry Round Table (STAIR) and Stem cell Therapeutics as an Emerging Paradigm in Stroke (STEPS) have developed guidelines imperative to successful trans- lation of stem cell treatments from the lab to the clinic [52-56]. Future work should focus on HUCB cell treatment which includes mannitol and NF-