Dr. Lyden continues a distinguished record of achievement in the field of cerebral vascular disease and stroke. He edited the book Thrombolytic Therapy for Acute Stroke, which received very favorable reviews and is now in its second edition. The book is unique in its inclusion of cases as tutorials designed to help the reader learn how to administer thrombolytic therapy.
Dr. Lyden's laboratory research focuses in two major areas: angiogenesis after ischemia, and mechanisms underlying the ischemic penumbra. His investigations have resulted in important new findings that have been described in numerous publications and presented at both national and international meetings. The Lyden lab developed a stereologic method for quantifying capillaries in the brain. To their surprise, they found that capillaries were not increased long term after focal brain ischemia. This suggests that post-ischemic angiogenic signaling serves some other purpose. They noted a short-term increase in capillarity around ischemic areas, and that such capillaries were always found in areas of necrosis: there was a significant correlation between capillary counts and macrophage numbers. This suggests a novel explanation for the post-ischemic angiogenic signaling, which the Lyden team terms the "clean-up hypothesis."
Dr. Lyden is currently pursuing microvessel quantification using novel two-photon laser scanning microscopy. This work is a collaboration with Professor David Kleinfeld, in the Physics Department, who is also a member of the Neurosciences Graduate Program. A second line of continuing investigation involves the mechanism of the formation of the ischemic penumbra. In classical models, the penumbra is viewed as a shell of marginally perfused tissue surrounding an ischemic core, or central zone of early cell death.
In contrast, imaging data obtained by Beth Friedman, PhD, in the Lyden lab clearly show the shell model to be invalid during the first few hours after stroke onset. Instead, Friedman found a heterogeneous pattern of blood-brain barrier damage and cellular injury: islands of injured tissue were intercalate among areas of normal tissue. The "islands" model of the ischemic penumbra has now been confirmed by other researchers using other methods. Friedman and Lyden continue to pursue studies designed to determine the mechanism of formation of the islands and the processes that cause the islands to coalesce over time, and to seek novel strategies that might interrupt the process.
The importance of Dr. Lyden's work and his recognition in the field are evident in long-term funding from pharmaceutical companies and in NIH-sponsored clinical trials, including R01, R21, and P50 grants from NINDS, a Merit Review from the VA, and Grants-in-Aid from the American Heart Association.
In addition, he is a sought-after lecturer both nationally and internationally. Dr. Lyden devotes a generous amount of time to teaching activities in a variety of settings. He serves as ward attending at the VA and UCSD Hillcrest and Thornton Medical Centers. He also attends in the VAMC and UCSD Urgent Neurology Clinics and in the UCSD Residents' Clinics as part of regular rotations.
Even with an intense research program, he spends significant time in scheduled instruction, specifically, Neurology 401 (Clinical Core Clerkship) and Neurology 407 (Elective Clerkship). He also coordinates a research seminar, Neurobiology of Cerebral Ischemia, and annually mentors one or two graduate and undergraduate students in his laboratory.
As a complement to a solid record of academic achievement, Dr. Lyden devotes substantial time to university and public service activities. In his capacity as Clinical Service Chief, he represents the department at the level of the UCSD Medical Group and Hospital. This position also has the designation of Department Vice Chair. In February 2007, Dr. Lyden began his term of service as Chair of the UCSD Health Sciences Faculty Council.
Editorial activities include service as a regular reviewer for such premier journals as Neurology, Stroke, and Journal of Stroke and Cerebrovascular Diseases. Additionally, he serves as an ad hoc reviewer for Archives of Neurology and Experimental Neurology. He is a member of the Editorial Board of the Journal of Stroke and Cerebrovascular Diseases and a charter member of the Editorial Board of the International Journal of Stroke.