Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide and can leave individuals with a range of functional challenges. Some complications of TBI include problems with speech and memory, as well as deficits in cognitive and motor abilities. After a TBI occurs, cells in the brain undergo what is known as an inflammatory cascade, a series of neuronal reactions following a brain injury that can contribute to lasting sensorimotor and cognitive impairments in individuals with TBI.
One of the many components involved in the inflammatory cascade are Krüppel-like factors (KLFs), proteins that help regulate numerous cell functions and protect neurons in the hippocampus during the event of TBI. Research shows that a specific type of KLF, known as KLF11, exhibits protective qualities during ischemic stroke. On the other hand, the genetic deletion of KLF11 can generally worsen neurobehavioral performance. However, the molecular mechanisms of KLF11 during brain trauma are largely unclear. To better understand the essential roles of KLF11, a team of researchers conducted a study on mice with KFL11 and those who were genetically modified to lack KFL11. The research team then studied differences in the mice’s cell regulation and inflammatory responses during TBI.
They determine that mice with the genetic deletion of KLF11 performed worse in various tests of sensory and motor abilities than mice with KLF11 after TBI. To assess learning and memory function, mice were tasked with navigating a maze—mice with TBI that did not possess KLF11 took longer to complete the maze than mice with KLF11. In addition to behavioral deficits, mice without KLF11 experienced a greater loss of brain tissue volume after TBI, supporting the idea that KLF11 has neuroprotective qualities during TBI. Finally, it was found that KLF11 genetic deletion promoted a pro-inflammatory state in the brain cells of mice in response to brain trauma.
There is abundant evidence that KLF11 plays a critical role in TBI, given the adverse behavioral and biological effects of KLF deletion. With a better understanding of the role of KLF11 in TBI, future research may consider its role in future drug therapies for improving recovery and quality of life.
Zhou C, Sun P, Hamblin M, et al. Genetic deletion of Krüppel-like factor 11 aggravates traumatic brain injury. Journal of Neuroinflammation. (November 2022).