HHV-6 infection elevates MMP-9 & TIMP-1 causing BBB dysfunction, febrile seizures

MMP-9 & TIMP-1 are highly elevated in patients with HHV-6 viremia causing dysfunction in the blood brain barrier: the cause of HHV-6 induced  febrile seizures?

A group led by Takashi Ichiyama in Japan has determined that serum levels of both matrix metallopreinase-9 (MMP-9) and tissue inhibitor of metalloproeinases-1 (TIMP-1) are significantly elevated in infants with HHV-6 infection compared to controls (P<0.05). The authors propose that the HHV-6 induced elevation in enzymes may cause dysfunction of the blood brain barrier, eventually leading to febrile seizures.

The matrix metalloproteinases are a family of enzymes that play an important role in inflammation. MMP-9 is a major component of the basement membrane of the cerebral endothelium and promotes the migration of cells through tissues and across the blood-brain barrier (BBB). The activity of MMP-9 is controlled in part by TIMP-1. The authors explain that TIMP-1 protects BBB function by inhibiting MMP-9 activity after brain injuries, thus reducing brain damage.

Although there appears to be a relationship between BBB dysfunction, HHV-6 infection and MMP-9 and TIMP-1, the authors were not able to suggest a clear mechanism of action. The authors have previously reported that elevated MMP-9 occurs in acute disseminated encephalomyelitis (ADEM), acute encephalopathy following prolonged febrile seizures and non-HSV limbic encephalitis, all conditions that have also been associated with HHV-6 infection.

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