Lymphotoxin-α Orchestrate Hypoxia and Immune factors to Induce Experimental Cerebral Malaria: Inhibition Mitigates Pathogenesis, Neurodegeneration, and Increase Survival.

Knockdown studies have shown lymphotoxin-α (Lt-α) as a critical molecule for Experimental cerebral malaria (ECM) pathogenesis. We investigated the role of lymphotoxin-α in regulating active caspase-3 and calpain1. T cell infiltration into the brains, and subsequent neuronal cell death are the essential features of Plasmodium berghei ANKA(PbA)-induced ECM.

Cytotoxic T Lymphocyte Granzyme-b mediates neuronal cell death during Plasmodium berghei ANKA induced experimental cerebral malaria.

Cerebral malaria is a complex, acute, neurological disease characterised by a sudden onset of cerebral symptoms. This disease is manifested as initial arousable stage that is followed by an unarousable coma and eventually death. Parasite burden and CD8+ T cell count in the brain determines the disease outcome.

Role of cytotoxic protease granzyme-b in neuronal degeneration during human stroke.

Infiltration of leukocytes into post-ischemic cerebrum is a well-described phenomenon in stroke injury. Because CD-8(+) T-lymphocytes secrete cytotoxic proteases, including granzyme-b (Gra-b) that exacerbates post-ischemic brain damage, we investigated roles of Gra-b in human stroke. To study the role of Gra-b in stroke, ischemic and non-ischemic tissues (from post-mortem stroke patients) were analyzed using immunoblotting, co-immunoprecipitation, terminal deoxy uridine nick end labeling (TUNEL) and Annexin-V immunostaining, and in vitro neuron survival assays.