Study maps how a stroke damages the blood-spinal cord barrier.

Delayed deterioration of neurological function after ischemia stroke is a well-documented clinical problem. However, minimal studies exist pertaining to spinal cord blood flow and blood-spinal cord barrier (BSCB) integrity with delayed neurological deterioration after transient spinal cord ischemia. Now, a study from researchers at the University of South Florida shows that stroke can cause long-term damage to the BSCB, creating a toxic environment in the spinal cord that may leave stroke survivors susceptible to motor dysfunction and disease pathology. The team state that their study, carried out using laboratory rats modelling stroke, demonstrates that ischemic stroke in both its subacute and chronic stages, damages the BSCB in a variety of ways, creating a toxic environment in the spinal cord that can lead to further disability and exacerbate disease pathology.

Previous studies show that the BSCB provides a specialized protective ‘microenvironment’ for neural cells in the spinal cord. The BSCB is the functional equivalent of the blood–brain barrier (BBB) in the sense of providing a specialized microenvironment for the cellular constituents of the spinal cord. Substantial vascular damage is a major pathologic feature of both subacute and chronic stroke caused by an extended period of microvascular permeability after the BSCB loses integrity. Damage to the BSCB plays a fundamental role in the development of several pathological conditions, including abnormal motor function. The current study evaluates post-stroke BSCB condition that might lead to the development of more effective therapies for stroke survivors.

The current study evaluated the BSCB in test animals at seven and 30 days after stroke modeling to show that ischemic stroke damaged the gray and white matter in the cervical spinal cord on both sides of the spinal column, based on analysis of electron microscope images. Results show damage to astrocytes, loss of motor neurons, reduced integrity of a tight junction protein between barrier cells, and swollen axons with damaged myelin in ascending and descending tracts connecting to the brain.

Data findings show that stroke-associated upregulation of Beclin-1 in endothelial cells composing the BSCB. Beclin-1, explain the group, helps induce autophagy, an activity associated with removal of various intracellular components. Results show a decrease in LC3B, an essential autophagy protein, at a later stage post-stroke. The lab state that these observations of Beclin-1 and LC3B suggest an impaired post-stroke autophagy process in spinal cord capillaries, inducing endothelial cell degeneration.

The researchers note that these stroke-related alterations in the cervical spinal cord indicate pervasive and long-lasting BSCB damage that would severely affect spinal cord function. They go on to add that the widespread microvascular impairment in the gray and white matter of the cervical spinal cord aggravated motor neuron deterioration and had the potential to cause motor dysfunction.

The team surmise that their data on BSCB damage in subacute and chronic ischemic stroke may lead to development of new therapeutic approaches for patients with ischemic cerebral infarction. For the future, the researchers state that the protein expression responsible for endothelial cell degeneration and tight junction damage identified in the study needs to be confirmed through further tests. They also plan to run behavioral tests of motor function in post-stroke animals with BSCB damage.

Source: University of South Florida