Dr.Susatyo P.Hadi,Sp.

S
Acute Ischemic Stroke

Role of Neuropeptides
in Neuroprotection
 Neuroscientific Perspectives
Result of investigations over the last 10 years
1. Brain ischemia triggers multiple cellular processes
2. Each process can be independently fatal
but also interlink
3. Are initiated or peak during reperfusion
(reperfusion injury), giving rise to :

Blaine C.White, Jonathon M.Sullivan, Donald J.DeGracia, Brian J.O’Neil, Robert

W.Neumar, Lawrence I.Grossman, Jose A.Rafols, Gary S.Krause. Brain Ischaemia and
reperfusion: molecular mechanisms of neuronal injury. Journal of the Neurological
Sciences 2000;179: 1-33.
Dr.J.Husada 11-2003
 Ischemic
Injury
Apoptotic
Cell Death
Necrotic
Cell Death

Dr.J.Husada 11-2003
Time Frames of Cellular Events
EAA

IEGs
PMN
ROS
Macrophages
CASPASES
Neurotrophins

min hours days

Dr.J.Husada 11-2003
 Spatial and Temporal Course of
Development of Ischemic Damage

O2 Adapted from :

1000 ATP Eugene G, Veronica I S ; “ Brain Ischemia”

Glu Kluwer Academic and Plenum Pub.
New York, 2003
Ca 2+
- depolarization
- energy failure
100 NECROSIS NEUROPROTECTION
- EXITOTOXICITY When……How?
- Spreading depression
- Disturbed ionic homeostasis

Ca-blockers Anti-ICAM INFLAMMATION

NMDA-blockers
10 Nos inhibitors
Caspase inhibitors
SOD mimetics
APOPTOSIS
N E U R O P E P T I D E S

minutes hours days weeks

Dr.J.Husada 11-2003
 Neuroprotection
• Against MULTIPLE pathologic biomolecular
processes triggered by cerebral ischemia
• The CNS has ENDOGENOUS defense
mechanisms that are modulated or regula-
ted by neuropeptides
• Other physiologic processes, should not be
affected I.e low incidence and harmless-
ness of side effects
• The agent should not interact with other
drugs usually used in regimen
• Safe even in high dosage administration
Dr.J.Husada 11-2003
 In Conclusion
1. Acute Ischemic Stroke is and should be
treated as a Medical Emergency
2. Major damage occurs in the first 3 hours
through multiple cellular processes
triggered by ischemia, and :
…starting or peaking during reperfusion
resulting in delayed cell death, and :
…continuing damage for days or weeks
even at 100% reperfusion
Dr.J.Husada 11-2003