The Plasminogen Activation System Promotes Dendritic Spine Recovery and Improvement in Neurological Function After an Ischemic Stroke

By the time you see your doctor in weeks/months/years s/he should already have figured out how to activate the Plasminogen Activation System. Because you need dendritic spine growth to advance your recovery. If your doctor doesn't have a protocol for that setup then you need to call the hospital president and ask WHAT THE HELL IS YOUR STROKE DOCTOR'S GOALS?

http://link.springer.com/article/10.1007/s12975-016-0454-x 

• Valerie Jeanneret
• , Manuel Yepes 

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Abstract

Advances in neurocritical care and interventional neuroradiology have led to a significant decrease in acute ischemic stroke (AIS) mortality. In contrast, due to the lack of an effective therapeutic strategy to promote neuronal recovery among AIS survivors, cerebral ischemia is still a leading cause of disability in the world. Ischemic stroke has a harmful impact on synaptic structure and function, and plasticity-mediated synaptic recovery is associated with neurological improvement following an AIS. Dendritic spines (DSs) are specialized dendritic protrusions that receive most of the excitatory input in the brain. The deleterious effect of cerebral ischemia on DSs morphology and function has been associated with impaired synaptic transmission and neurological deterioration. However, these changes are reversible if cerebral blood flow is restored on time, and this recovery has been associated with neurological improvement following an AIS. Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) are two serine proteases that, besides catalyzing the conversion of plasminogen into plasmin in the intravascular and pericellular environment, respectively, are also efficient inductors of synaptic plasticity. Accordingly, recent evidence indicates that both, tPA and uPA, protect DSs from the metabolic stress associated with the ischemic injury, and promote their morphological and functional recovery during the recovery phase from an AIS. Here, we will review data indicating that plasticity-induced changes in DSs and the associated post-synaptic density play a pivotal role in the recovery process from AIS, making special emphasis on the role of tPA and uPA in this process.

Clot dissolver tPA's tardy twin could aid in stroke recovery

Maybe in another 50 years we'll have another stroke drug. But this won't occur unless you start screaming at your doctor to push for clinical trials on this. It sounds more like it fixes one or more of the problems in the neuronal cascade of death.
http://medicalxpress.com/news/2014-10-clot-dissolver-tpa-tardy-twin.html
Researchers at Emory University School of Medicine have identified a protein released by neurons while the brain is recovering from a stroke.

The results are scheduled for publication Oct. 21 in Journal of Neuroscience.
The protein, called urokinase-type plasminogen activator or uPA, has been approved by the FDA to dissolve blood clots in the lungs. It has been tested in clinical trials in some countries as a treatment for acute stroke.
The Emory team's findings suggest that in stroke, uPA's benefits may extend beyond the time when doctors' principal goal is dissolving the blood clot that is depriving the brain of blood.
Instead, uPA appears to help brain cells recover from the injuries induced by loss of blood flow. Treating mice with uPA after an experimental stroke can improve their recovery of motor function, the researchers found.
uPA (urokinase-type plasminogen activator) and tPA (tissue-type plasminogen activator), the drug that is the only approved treatment for acute stroke, have similar names, because they both act biochemically to activate plasmin, which directly dissolves blood clots.
"We are finding that uPA and tPA do very different things in the brain. We see that uPA is released during the recovery phase of a stroke over several hours," says lead author Manuel Yepes, MD, associate professor of neurology at Emory University School of Medicine. "This is in sharp contrast with tPA, which is released from neurons within milliseconds of hypoxia or ischemia [loss of blood flow]."
Co-first authors of the paper are postdoctoral fellows Fang Wu, PhD, and Ramiro Echeverry, MD, and pregraduate student Marcela Catano.
The Emory team found that mice that lack uPA do not regain as much forelimb strength after a one hour blockage of the middle cerebral artery, compared with control mice. This suggests that uPA produced within the brain is promoting recovery. In addition, immediate treatment with supplementary uPA after a stroke can boost the recovery of forelimb strength, the researchers found.
uPA does not have a direct effect on neurons when they are being deprived of oxygen and nutrients. Rather, uPA appears to help remodel dendritic spines, structures on neurons that are critical for communication. After a stroke, dendritic spines are replaced by swelling on neurons that survive but are close to the damaged area of the brain.
In cultured neurons, uPA can induce the re-emergence of dendritic spines after toxic injury that mimics the effects of a stroke. uPA seems to help the neurons' internal skeletons reorganize. The part of the uPA protein that acts in dissolving blood clots is not necessary for this effect, but uPA's interaction with its receptor uPAR is required.
Yepes says his team is testing whether treatment with uPA can still provide benefits in mice when it is given some time after an experimental stroke, which could provide some hints as how it could best be used clinically.