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Development of treatment for spasticity after stroke

  • School of Medicine/Graduate School of Medicine
  • Department of Physical and Occupational Therapy
  • Physical Therapy

Lee Sachiko [Associated Professor]

http://www.lee-lab.com

Outline of Seeds

Spasticity is one of the subsequent complications associated with injuries to the central nervous system, among them cerebral infarction, spinal cord injury, multiple sclerosis, and cerebral palsy. Spasticity is defined as aggravated symptoms of a velocity-dependent increase in muscle tone in other words, it involves the involuntary muscle contraction when the person moves a joint. Spasticity is said to be a result of the hyperexcitability spinal reflex, but details about the mechanism that brings this spinal reflex aggravation about are unknown. Current spasticity treatments covered by insurance include baclofen, a drug that inhibits motor neurons in the spinal cord, and botulinum toxin injections, which inhibit muscular contractions themselves by targeting neuromuscular junctions. Despite the fact that they require rehabilitation necessary in order to recover voluntary motor functions, treatment of these functions is blocked by the fact that the drugs inhibit contractions of the muscles suffering from spasticity. The aforementioned treatment methods are not radical therapies either, which limits their effectiveness. To make further progress, we need to develop treatments that target the mechanism creating the spasticity itself. Our research team is using mouse models exhibiting spasticity as a result of cerebral infarction in order to study the underlying mechanism that triggers spasticity. We are also working on developing new spasticity treatments that do not inhibit voluntary muscle contractions.

Novelty and originality of this research

We are leading the world in establish of mouse models exhibiting spasticity as a result of cerebral infarction. In the past, reports on spasticity-triggering mechanisms were primarily carried out at the spinal level, but our mouse models allow us to analyze neuronal spasticity changes in higher nerve regions. By focusing especially on the aggravated status of neural activity in the brainstem reticular formation region that forms the core of the spinal reflex, we are discovering the possibility that spasticity stem from abnormalities in other regions of the brain, rather than in the spinal cord alone. We are currently analyzing (1) changes in neural activity across broad regions of the brain with MRI images that use manganese-based contrasts during spasticity induction and (2) the involvement of homeostatic plasticity changes on the status of aggravated neural activities in order to develop new radical spasticity treatments that align with the goals of rehabilitation therapies. We are also working to develop treatments that control the reflexes without inhibiting voluntary muscle contractions for spasticity that are becoming chronic and/or objectionable . These treatments would also be ideal for use in conjunction with rehabilitation therapies.

Application and research area for Industry collaboration

Though we are only at the basic research stage, we are currently looking into magnetic stimulation and other non-invasive methods in order to develop radical spasticity treatments. Because simple devices are necessary for actual hospital treatment settings, we are hoping to create an industrial-academic partnership that will allow for joint development of such equipment. We are also looking to develop new drugs that can control the reflexes without inhibiting voluntary muscle contractions for spasticity that are becoming chronic and/or objectionable. Because we are currently in the process of targeting and discovering receptors, we expect to be able to develop a new drug that is both cheap and safe. We also need to look into the possibilities of adverse reactions in healthy muscle, but if drug administration is possible through skin penetration, it would be easy on patients and easy to use in conjunction with rehabilitation therapies. We are seeking out industrial-academic collaboration in order to develop these ideas further.

Key Takeaway

Spasticity is reported in approximately 40% of patients following cerebral infarction, and research on spasticity treatments along with motor paralysis is needed. Although it will still take time to progress to the clinical research stage from our current basic research phase, we believe that our studies address pressing needs in clinical settings.

Keywords

Spasticity, cerebral infarction, rehabilitation