Pathogenesis of Neurotrauma and Stroke

The disease initiated by neurotrauma; spinal cord injury (SCI), traumatic brain injury (TBI) and severe concussion, and stroke has been recently elucidated by Dr. Kwiecien in his systematic studies on the rat model of the SCI.  A trauma to the spinal cord initiates a severe, destructive and extraordinarily protracted inflammation confined to a cavity of injury (COI) but continually damaging the surrounding spinal cord for a long time, >16 weeks.  The white matter injury in the SCI result in large quantity of damaged myelin, a very immunogenic, pro-inflammatory material targeted by phagocytic macrophages and contributing to a mechanism of the vicious cycle producing such protracted disease with destructive severity.  Inflammatory damage to blood vessels in the surrounding spinal cord causes a chronic vasogenic edema persisting along the active inflammation, >16 weeks removing function from swollen spinal cord thus preventing recovery of lost function.  Although stroke does not originate from neurotrauma but rather from a sudden occlusion of a large cerebral blood vessel, resulting ischemia and myelin-rich tissue necrosis initiates a similar disease. 

Neurologic deficits are related to:

  1. Destruction of the spinal cord at the time of neurotrauma

  2. Destruction of the spinal cord by the severe inflammation after neurotrauma

  3. Persistence of the vasogenic edema


Altogether, neurotrauma and stroke initiate a devastating disease for which effective treatments are not available.  Unmet but absolutely desperate global market is estimated to exceed $400B a year and constitutes the largest market for a medical treatment ever.

Every year, the SCI occurs in 500-700 thousand people around the world; primarily young male adults, victims of automobile accidents, battle and also falls in elderly.  These considerable numbers have tendency to increase and the medical and social costs related to treating, hospitalization and care for the SCI patients are very high.  TBI is more common, at >2.5M/year, severe concussion >5M/year, stroke >15M/year.

A Canadian study published in 2013 indicates that the cost of post-SCI hospitalization among ~1,400 SCI patients averaged $2M and the remaining life-time health costs ranged from $1.5-3.0M with the higher cost related to the need for the continuous use of artificial respirator in patients with higher neck fractures.  An estimation in 2025 suggests that in Ontario with 40% of national population the total annual cost for treatment of new cases of SCI approximates $10B constituting a large position in the annual OHIP (Ontario Health Insurance Plan) budget.

Treatment of Acute Spinal Cord Injury

(updated July 24, 2025)

In recent months a SCI patient admitted to a hospital at the Medical University of Lublin, Poland, was diagnosed with high (C6) neck vertebral fracture, quadriplegic and unable to breath on his own, therefore connected to a respirator via transtracheal tube. To this patient Dr. Wojciech Dabrowski, Professor and Chair, Department of Anaesthesiology and Intensive Care, MUL, administered experimentally hop xanthohumol (a clinical study registered with NIH and approved by The Ethics Committee at MUL) at an optimal dose previously established by Dr. Kwiecien in preclinical studies. After 10 days of continuous treatment, this patient regained his breathing and was detached from the respirator. Moreover, while lying in bed, he lifted either arm and either leg up.  An MR image of the spinal cord lesion showed no edema (swelling) in the spinal cord around the lesion indicating that the anti-inflammatory effect of treatment allowed for clearance of excess fluid from un-damaged part of the spinal cord corresponding to the restoration of locomotor function.  Nine more SCI patients treated by Dr. Dabrowski to date, all showed improvement in neurologic deficits.

 

VPC NeuroTherapeutics Inc., performed extensive preclinical studies on anti-inflammatory effect of xanthohumol (proprietary) in SCI models leading to establishment of the optimal dose that was then translated into a human dose using an FDA developed coefficient.

 

Further work on synthesized xanthohumol is progressing towards clinical trials on the lead treatment by VPC NeuroTherapeutics Inc., called VPCnt-101.