Characterising maladaptive axonal and intrinsic plasticity in the sub-acute phase post stroke — The Association Specialists
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Characterising maladaptive axonal and intrinsic plasticity in the sub-acute phase post stroke (21797)

Emily King 1 2 , Jamie L Beros 1 2 , Hakuei Fujiyama 3 4 5 , John N.J Reynolds 6 , Alex D Tang 1 2
  1. The university of Western Australia, Crawley, WESTERN AUSTRALIA, Australia
  2. Perron Institute for Neurological and Translational Sciences, Nedlands, Western Australia
  3. School of Psychology, Murdoch University, Perth, WA, Australia
  4. Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, WA
  5. Centre for Healthy Ageing, Health Futures Institute, Murdoch University, Perth, WA, Australia
  6. Department of Anatomy and the Brain Health Research Centre, The University of Otago, Dunedin, New Zealand

Stroke is a leading cause of disability and stroke-induced changes in cortical excitability are thought to impede functional recovery. Identifying cellular targets that contribute to maladaptive excitability holds great potential for developing new therapeutic interventions to improve stroke outcomes.

One potential target is the axon initial segment (AIS), the site of action potential initiation in neurons. In the acute phase post-stroke, neurons in the peri-infarct zone display abnormal AIS structural properties which may contribute to altered neuronal excitability. However, whether this continues into the sub-acute phase post-stroke, a period with heightened plasticity and when physical rehabilitation typically begins, is unknown.

Here, we induced an ischemic stroke to the motor cortex alongside virus labelling of pyramidal neurons in the peri-infarct zone and contralesional hemisphere in mice. Immunofluorescence and patch clamp electrophysiology measurements were made 28-days later to assess changes in AIS structure and function. Additionally, we investigated hemispheric-, layer-, and sex-dependent differences in AIS and intrinsic membrane properties.

We found AIS structure and function was preserved in the sub-acute phase post-stroke. However, input resistance was reduced across both hemispheres and evoked spike firing frequencies were reduced in the peri-infarct zone in both sexes. In addition, we found stroke reduced evoked firing frequencies in the contralesional hemisphere of male mice only, suggesting sex-dependent differences in neuronal function post-stroke.

These findings highlight intrinsic excitability as a contributor to the dysregulation of cortical excitability observed in the sub-acute phase post-stroke and supports the need to develop sex-specific treatments to improve stroke outcomes.