Dr. Johnston and his group, including Drs. Mary Blue, Mary Ann Wilson and Alec Hoon, perform clinical and basic laboratory research focused on developing therapies to reduce brain injury in infants and children, as well as to promote recovery by enhancing brain plasticity. His laboratory was one of the first to describe the mechanisms through which the neurotransmitter glutamate triggers brain injury from lack of oxygen, trauma and other insults. If administered early enough, drugs that block the effects of glutamate on one of its receptors called the NMDA receptor can totally prevent brain injury in infants. His group also recognized that the major role that glutamate plays in injury during development is related to the important role it plays in normal development. During development, glutamate released from nerve terminals helps to refine the synaptic connections that link neurons into circuits. These mechanisms are enhanced during development to shape circuits in response to environmental stimuli and formation of memories, a process called neuronal plasticity. When the brain is injured, these circuits can be damaged by too much glutamate, much like a computer's chips can be damaged by a power surge during a thunderstorm. Because injury and plasticity are two sides of the same processes in brain development, Dr. Johnston's research has grown beyond mechanisms of injury into processes that control brain plasticity. For example, he studies how the cerebral cortex is reassigned in response to injury, which is the major mechanism for recovery of function from stroke and other disorders. Even learning and long-term memory are based on these same mechanisms since it depends on neurons exciting each other with glutamate and changes in synaptic connections. Numerous disorders associated with intellectual disabilities are caused by genetic flaws in these systems, and Dr. Johnston recently completed a project focused on a defect in a neuronal signaling process involved in a form of X-linked intellectual disability. Dr. Johnston's initial pursuit of ways to reduce brain injury in infants and children with medications has led to a broader understanding of processes involved in plasticity and recovery from injury. The immature brain's glutamate signaling system, with its complex neuronal circuitry, proves to be especially vulnerable to injury. Accordingly, Dr. Johnston's research has proved to be relevant to a broad range of neurodevelopmental disabilities including cerebral palsy, intellectual disabilities, genetic metabolic disorders, and epilepsy, as well as brain injury from trauma and lack of oxygen.
A Diagnostic Approach for Cerebral Palsy in the Genomic Era.
Lee RW, Poretti A, Cohen JS, Levey E, Gwynn H, Johnston MV, Hoon AH, Fatemi A.
Neuromolecular Med. 2014 Oct 4. [Epub ahead of print]
Potential for treatment of severe autism in tuberous sclerosis complex.
Gipson TT, Gerner G, Wilson MA, Blue ME, Johnston MV.
World J Clin Pediatr. 2013 Aug 8;2(3):16-25. doi: 10.5409/wjcp.v2.i3.16. eCollection 2013 Aug 8. Review.
Cognitive and functional impairment associated with care in the PICU*.
Pediatr Crit Care Med. 2014 Sep;15(7):676-7. doi: 10.1097/PCC.0000000000000231. No abstract available.
Early neurodevelopmental screening in tuberous sclerosis complex: a potential window of opportunity.
Gipson TT, Gerner G, Srivastava S, Poretti A, Vaurio R, Hartman A, Johnston MV.
Pediatr Neurol. 2014 Sep;51(3):398-402. doi: 10.1016/j.pediatrneurol.2014.04.028. Epub 2014 May 4.
Systemic Injection of CD34+-Enriched Human Cord Blood Cells Modulates Poststroke Neural and Glial Response in a Sex-Dependent Manner in CD1 Mice.
Kadam SD, Chen H, Markowitz GJ, Raja S, George S, Shotwell E, Loechelt B, Johnston MV, Kamani N, Fatemi A, Comi AM.
Stem Cells Dev. 2014 Sep 23. [Epub ahead of print]