Neuroscience Graduate Group

Pathophysiology of Neuroinflammation and Infection in the CNS

Tuesday and Thursday 10:30am until noon; begins March 18, 2008
Barchi Library (140 John Morgan Building)

Course Directors: Dennis Kolson, MD, PhD and Kelly Jordan-Sciutto, PhD
Textbook: None. Readings will all be from the primarily literature.

Course summary

This module will address common CNS inflammatory and infectious diseases from the standpoints of clinical neurological syndromes and current basic scientific research in mechanisms of pathogenesis. Among the common CNS infections faced by neurologists, HIV and other viral infections of the brain (particularly herpes simplex virus and measles) can cause either subacute or chronic debilitating neurological syndromes that offer particular challenges for diagnosis and treatment. Other serious CNS infections include bacterial and viral meningitis, abscesses, lyme infection, and syphilis. Often the clinical presentation is highly variable for each of these, and diagnosis depends upon careful clinical, neuroradiographic and serological testing. Bacterial infections are one example where mechanisms of tissue entry and induction of pathological immune and cellular responses have been intensively investigated at a basic science level, leading to discovery of new therapeutic interventions. Similar research has led to adjunctive therapy for HIV infection of the CNS.

Non-infectious inflammatory CNS diseases offer similar diagnostic and therapeutic challenges. Examples of such diseases include multiple sclerosis and paraneoplastic diseases associated with autoimmunity against native or tumor-associated antigens. The clinical syndromes are well-characterized, but the pathogenesis of each remain incompletely understood. We will discuss interesting clinical aspects as well as current research into the mechanisms of neurodegeneration associated with these syndromes.

Goals include

  1. To understand the basic clinical manifestations and mechanisms of neuronal degeneration in CNS HIV infection
  2. To understand how neuroimmune responses to virus infection in the CNS can cause pathological damage, using specific neurotropic virus models
  3. To understand basic mechanisms of bacterial CNS pathogenesis
  4. To recognize common neurologic paraneoplastic syndromes and basic immune mechanisms for such syndromes
  5. To understand clinical manifestation of primary autoimmune CNS demyelination and the underlying autoimmune basis for CNS demyelination

Lectures will commonly cover

  1. clinical presentation and epidemiology (~10 min)
  2. physiological and pathophysiological mechanisms, including biological mechanisms in common with other diseases/ disorders/ conditions (40-45 min)
  3. current therapies AND/OR strategies for developing future therapies: the role of "translational research"; design and conduct of patient-oriented research AND/OR any relevant ethical issues in clinical research, and/or ethics of particular clinical trial designs in specific patient populations (~10 min)
  4. patient visits (when possible)

Class format

"Typical" class format:
60 min: faculty lecture
30 min: informal discussion by students of assigned review paper with course directors leading discussion. Students must submit 2 questions 2 days in advance by posting them on the electronic bulletin board (see "requirements and grading".)
Occasionally patients will attend to give their perspective and answer student question.

Class format on student presentation days:
During 3-4 class sessions students will present primary research papers (see "requirements and grading".)

Requirements and grading

In addition to course attendance,
a) submission of discussion questions: students must submit, via the electronic bulletin board , two questions about each assigned paper. A paper will be assigned for approximately 10 of the 14 class sessions. Questions must be posted to the electronic bulletin board at least 2 days in advance of the session during which the paper will be discussed; questions will be used as the basis for in-class discussions.
b) consistent participation in the discussions that will each lecture
c) quality of presentations: each student will make one or two 45-minute presentations during the course. The papers will be assigned at last 1 week in advance and students will work in pairs to prepare and present their paper(s). Each presentation is expected to address: background, data, description of technical methods used, results, questions the study answered and those it left unanswered, critique and/or questions for discussion, possible future directions.


Lectures - spring 2008

Lecture Title Lecturer Date
HIV Neuropathogenesis: virology, pathology and mechanisms of excitotoxicity Dennis L. Kolson, MD, PhD March 18, 2008
Multiple Sclerosis: pathogenesis Clyde Markowitz, MD March 20, 2008
HIV Neuropathogenesis: roles for cell cycle proteins and transcription factors Kelly Jordan-Sciutto, PhD March 25, 2008
Herpes virus and the CNS: virus latency Claude Krummenacher, PhD March 27, 2008
Arbovirus encephalitis: virology, pathology and neurodegeneration Samantha Soldan, PhD April 1, 2008
Use of Viral Vectors in CNS-derived cells Deborah Watson, PhD April 3, 2008
Interactions between the Immune and Nervous Systems Katalin Kariko, PhD April 8, 2008
Student Presentations A Vaccine for Alzheimer's Disease? April 10, 2008
Neuroimmunology of measles virus infection of the CNS Glenn Rall, PhD/Virginia Young, PhD April 15, 2008
TBD TBD April 17, 2008
Bacterial meningitis Amy Pruitt, MD April 22, 2008
TBD TBD April 24, 2008
Paraneoplastic syndromes affecting the nervous system Josep Dalmau, MD April 29, 2008
TBD TBD May 1, 2008