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Veeravalli Stroke and Spinal Cord Injury Lab

A graphic illustration of 2 brightly colored protein strands.
This illustration depicts the interaction of MMP-12 with tPA. The protein on the right is MMP-12, while the protein on the left is tPA.

The Veeravalli lab focuses on explaining cellular and molecular mechanisms of tissue damage and functional recovery, identifying and validating novel targets, and evaluating the efficacy of novel treatments to reduce tissue damage and improve functional recovery after stroke and spinal cord injury.

Areas of Focus

The research team investigates the efficacy of novel treatments to:

  • Reduce brain or spinal cord injury, inflammation, apoptosis, and demyelination
  • Prevent blood-brain barrier or blood-spinal cord barrier disruption
  • Preserve neurological function
  • Promote the recovery of sensorimotor and cognitive function in rodent models of ischemic stroke and spinal cord injury.

The research goals are met through the use of multiple treatment strategies, including cell-based therapy with mesenchymal stem cells, target gene silencing therapy with siRNA/shRNA, and recombinant antibody therapy using single-chain variable fragment (scFv) antibodies.

Lab News

Veeravalli Lab welcomes Isidra M. Baker

Veeravalli Lab welcomes Isidra M. Baker

Posted on October 02, 2024

Isidra M. Baker joined the Veeravalli Lab as a Research Specialist on October 1, 2024, after earning her MS degree in Biotechnology from the University of Illinois College of Medicine Rockford in 2024.

Meet the Research Team

Lab Director and Henderson Professor in Neuroscience Research
Krishna Kumar Veeravalli
Lab Director and Henderson Professor in Neuroscience Research
Associate Professor
Jeffrey D. Klopfenstein
Associate Professor
Research Assistant Professor
Siva Reddy Challa
Research Assistant Professor
Professor
Dzung Dinh
Professor
Professor of Clinical Pathology
David M. Pinson
Professor of Clinical Pathology
Instructor
Casimir A. Fornal
Instructor
Research Specialist
Isidra Baker
Research Specialist

Stroke Projects

Stroke+Control shRNA treatment and Stroke+tPA shRNA treatment
Source: Figure 6A from Challa et al., Experimental Neurology 2024; 374: 114727

We discovered that MMP-12 upregulates several folds higher than any other MMPs after transient focal cerebral ischemia and reperfusion (I/R). In addition, our lab reported for the first time the deleterious role of elevated MMP-12 in pathogenesis after cerebral I/R. Attenuation of MMP-12 expression in the ischemic brain reduced infarct volume and BBB disruption. Also, MMP-12 suppression attenuated inflammation, apoptosis, and demyelination and improved the neurological and functional recovery following cerebral I/R. Our studies to date validate MMP-12 as a promising therapeutic target for acute ischemic stroke treatment.
To obtain a significant therapeutic benefit, it is essential to control both the early and delayed brain injury in the core as well as the penumbra following cerebral I/R. By utilizing shRNA-mediated gene-silencing technology, we identified several important targets that are detrimental and had a key role in the pathogenesis of inflammation, apoptosis, and demyelination following cerebral I/R.

Our work has increased the understanding of molecular mechanisms underlying the neuroprotection offered by mesenchymal stem cells (MSC) treatment after cerebral I/R. MSC treatment attenuated apoptosis and the induction of apoptotic and DNA damage signaling and facilitated the DNA repair mechanisms. Moreover, MSC treatment prevented the induction of MMPs and facilitated neurological recovery after cerebral I/R. Interestingly, treatment with exosomes obtained from MSC at experimental conditions that closely mimic human cerebral I/R improved the outcomes.

Many of our publications that substantiate the above description are listed below.

Spinal Injury Projects

3 images side by side, depicting a normal rat spinal cord, an injured rat spinal cord and a hUCB treated rat spinal cord.
Source: Figure 6A from Veeravalli et al., Neurobiology of disease 2009; 36: 200
Outcomes of hUCB treatment in rat spinal cords.

SCI is a devastating injury which involves an initial mechanical damage followed by a series of cellular and molecular secondary events resulting in the progressive destruction of spinal cord tissue. Neuropathic pain (NP) is one of the most debilitating sequelae of neurotrauma and remains an unmet clinical need for at least 40% of patients with SCI. Methylprednisolone is the only FDA approved drug that is currently available to limit the extent of SCI in the acute settings but it does nothing for prevention or mitigation of subsequent neuropathic pain following SCI. Despite decades of extensive research in this area, no clinically effective therapies exist to modulate neuropathic pain and facilitate functional recovery after spinal cord injury.

SCI results in a multitude of changes affecting several different cell types, leading to a complex pathological picture. Most research findings to date suggest that no single therapy will be sufficient to overcome the myriad of biological cascade initiated after SCI. Effective treatments of SCI require a multifaceted approach using a combination of different methodologies and therapeutic approaches over different time to address many of the devastating issues besides functional impairment such as chronic pain associated with SCI.

Stem cell transplantation and gene silencing

Our current research utilizes stem cell transplantation and gene silencing. A variety of different stem cell types have been evaluated in animal models and humans with SCI. Previous studies have reported that human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) promote neural repair after SCI, even when administered 5 days after injury. Transplanted hUCB-MSCs differentiate into various neural cells and induce motor function improvement in SCI rat models. In concert with these findings, we also have recently reported that hUCB-MSCs improved the locomotor recovery of spinal cord injured rats while regulating the expression of several genes related to apoptosis, axon outgrowth and myelin degradation. However, more detailed experiments are needed to delineate the mechanism of how hUCB-MSCs modulate NP and functional improvement after SCI.