McMaster University

McMaster University

Jacek M. Kwiecien

, PhD, DVM

Assistant Professor (Part-Time)
Pathology and Molecular Medicine

McMaster University
Central Animal Facility
1U22D Health Sciences Centre
905-525-9140 ext. 22827
kwiecien@mcmaster.ca

Administrative Assistant: Lisa Bulger

Jacek M. Kwiecien

Faculty Biography

Education and Professional Standing

  • PhD Veterinary Pathology, University of Guelph, 1995
  • MSc Veterinary Pathology, University of Guelph, 1991
  • DVM, University of Agriculture (Poland), 1983

Interests

Research and Clinical Focus

By training a veterinarian, veterinary pathologist, comparative neuropathologist and neuroscientist, I conduct studies examining cellular events taking place in the functional regeneration in the adult central nervous system (CNS). For my research I use unique rat models devoid of myelin, an insulator along the nerve processes (axons) which is necessary for proper function in axons. Loss of myelin, particularly well known in Multiple Sclerosis, brain and spinal cord injury, results in permanent and devastating neurologic deficits in human patients.  Although massive damage to myelin such as in the spinal cord injury leads to a very destructive and chronic pathology called leukomyelitis, temporary removal of myelin from a targeted area of white matter can lead to axonal plasticity and their regeneration.

In an international collaborative effort we focus on analyzing pathology of natural progression of the spinal cord injury, a still poorly understood and intractable disease.  We strive to understand the disease, to effectively treat it and to monitor its progress by developing imaging modalities suitable to observe pathologic changes in experimental animals and then in patients.

Trauma to white matter as is common I the spinal cord injury results in a bi-phasic course of pathology; an initial acute tissue damage involves acute vascular events including hemorrhage, edema and ischemia that lead to cell necrosis and acute pro-inflammatory pathways.  This distinct phase lasts >48 hrs in the rat model and has been extensively studied by others.  It is followed by a phagocytic inflammatory phase where a pure population of macrophages target damaged myelin and in mechanism of vicious cycle destroys myelin and tissue in areas adjacent to the site of injury leading to more macrophage chemotaxis.  A cystic cavity forms and grows where this process is localized but persists for many weeks until it dies out and a large cyst filled with cerebrospinal fluid replaces the tissue of the spinal cord with irreversible loss of tissue and neurological function.

We inhibited leukomyelitis with subdural infusion of a high dose of dexmethasone into the vicinity of the site of injury in experimental rats.  Effectively, we stopped the progression of the destruction of the spinal cord and thus inhibited the loss of the neurologic function.  Currently, using a balloon crush rat model we are working on optimizing the treatment with subdural infusion of dexamethasone.

Since the spinal cord injury remains a poorly understood disease from pathology stand point, we conduct a systematic study analyzing histological changes in the spinal cord from day 1 to week 16 post-balloon crush in parallel with MRI scanning of the lesions.  This large study will serve to understand how inflammatory damage of the spinal cord tissue occurs, what is the compensatory reaction of the tissue and how and when leukomyelitis is extinguished in a natural fashion.  Utilizing MRI scan supported by parallel histopathology will allow to develop accurate interpretation of MR images in longitudinal studies in preclinical and then in clinical studies on novel treatments.

Once the severity of leukomyelitis is successfully inhibited, designs for neuroregeneration of the white matter loss in the spinal cord injury accident can be executed.

Affiliations with Research Centres

While the mutant dysmyelinated rats are bred and raised at McMaster University, and neurosurgeries are performed at McMaster as well, some tissues are analyzed in excellent laboratories around the continent specializing in studies on CNS regeneration.

My research collaborators include investigators from:

  • Sunnybrook Research Institute, Toronto, Ontario, Canada
  • Medical University of Lublin, Poland
  • The Academy of Sciences of the Czech Republic, Prague

Research Goals

  • Mechanisms of leukomyelitis ina spinal cord injury model
  • Pharmacol;ogical inhibition of leukomyelitis
  • Magnetic Resonance Imaging of the spinal cord injury

Noteworthy Accomplishments

The development of animal models of:

  • Pathology of spinal cord injury
  • MR imaging of spinal cord injury
  • Subdural infusion for pharmacological intervention in spinal cord injury

Team Members

 

Selected Publications

  • Kwiecien JM, Avram R. Long distance axonal regeneration in the filum terminale of adult rats is regulated by ependymal cells. Journal of Neurotrauma 2008, 25: 196-204.
  • McPhail LT, Borisoff JF, Tsang B, Hwi LP-R, Kwiecien JM, Ramer MS. Protracted myelin clearance hinders central primary afferent regeneration following dorsal rhizotomy and delayed neurotrophin-3 treatment. Neuroscience Letters 2007, 411: 206-211
  • Scott ALM, Ramer LM, Soril LJJ,Kwiecien JM, Ramer MS. Targeting myelin to optimize plasticity of spared spinal axons. Molecular Neurobiology 2006, 33: 91-111.
  • Eftekhapour E, Karimi-Abdolrezaee S, Sinha K, Velumian AA, Kwiecien JM, Fehlings MH. Structural and functional, alterations in spinal cord axons in adult Long Evans Shaker (LES) dysmyelinated rats. Experimental Neurology 2005, 193: 334-349.
  • McPhail LT, Stirling DP, Tetzlaff W, Kwiecien JM, Ramer MS. The contribution of activated phagocytes and myelin degeneration to axonal retraction/dieback following spinal cord injury" European Journal of Neuroscience 2004, 20: 1984-1994.
  • Phokeo V, Kwiecien JM, Ball AK. Characterization of the optic nerve and retinal ganglion cell layer in the dysmyelinated adult Long Evans Shaker rat: possible axonal sprouting. Journal of Comparative Neurology 2002, 451: 213-224.
  • Kwiecien JM, Blanco M, Fox JG, Delaney KH, Fletch AL. Neuropathology of bouncer Long Evans, a novel dysmyelinated rat. Comparative Medicine 2000; 50: 503-510.
  • O’Connor LT, Goetz BD, Kwiecien JM, Delaney KH, Fletch AL, Duncan ID. Insertion of a retrotransposon into the myelin basic protein gene causes CNS dysmyelination in the Long Evans shaker (LES) rat. Journal of Neuroscience 1999; 19: 3404-24-13.
  • Kwiecien JM, O’Connor LT, Goetz BD, Delaney KH, Fletch AL, Duncan ID. Morphological and morphometric studies of the dysmyelinating mutant, the Long Evans shaker rat. Journal of Neurocytology 1998; 27: 581-591.
  • Delaney KH, Kwiecien JM, Wegiel J, Wisniewski HM, Fletch AL. Familial dysmyelination in a Long Evans rat mutant. Laboratory Animal Science 1995; 45: 547-553.
  • Kwiecien JM, Delaney KH.  Endpoints in myelin deficient (md) rat:  Acute hemorrhagic myelitis attributed to spinal hyperflexion and vertebral fracture.  Comparative Medicine  2010, 60: 343-347.
  • Kwiecien JM.  Cellular mechanisms of white matter regeneration in adult dysmyelinated rat model.  Folia Neuropathologica  2013, 51: 189-202.
  • Oakden W, Kwiecien JM, O’Reilly MA, Lake E, Akens MK, Aubert I, Whyne C, Hynynen K, Stanisz GJ.  A non-invasive model of cervical spinal cord injury induced with focused ultrasound.  Journal of Neuroscience Methods 2014, 235: 92-100.
  • Kwiecien JM, Jarosz B, Machova-Urdzikova L, Rola R, Dabrowski W.  Subdural infusion of dexamethasone inhibits leukomyelitis after acute spinal cord injury in a rat model.  Folia Neuropathologica (in press).
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