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DEFINITION OF

STROKE

The definition of a Stroke (WHO Stroke,


1989) is as follows:
Rapidly developing disturbance of cerebral
function
focal (or global)
with symptoms lasting 24 hours or longer or
leading to death,
with no apparent cause other than that of
vascular origin.
2= cytokines

1=Ischemic cascade

Gene
Regulation of injury

APOPTOSIS
(CASPASE)
3=cascade of apoptotic events
ISCHEMIA
(necrotic
cell death)

(apoptosis :programmed
cell death) Caspase
(caspase apoptosis: programmed cell dea

(necrosis)

ISCHEMIC CORE AND ISCHEMIC PENUMBRA


(Friedlander 2003)
GLUCOSE FUELS ION PUMPS
ATP-ase dependent membrane pumps Ca++ out + Na+
ut
M
I
T
3
O
C
H
O
NDRIA
1 2

CALCIUM HOMEOSTASIS
1. ATP-ase dependent membrane Ca++out; Na+ in/out; K+
in.
2. Glutamate in Ca++ in via NMDA.
3

1 2

CA++ HOMEOSTASIS DURING ISCHEMIA


1. Ca++ in; Na+out 2. Na+ out; glutamate out 3. Ca++ uptake by
mitoch &
PRESYNAPTIC POSTSYNAPTIC

VSCC VSCC

PRE-AND POST SYNAPTIC VOLTAGE SENSITIVE


CHANNELS
NMDA is blocked by Mg++, but voltage dependent. AMPA activation & Na+ influx
depolarisation
++ ++ + -
1
1
7

3
3

4
4

6
5

INTRACELLULAR Ca++ DURING ISCHEMIA CELL DAMAGE & CELL


DEATH
PLC= phospholipase C; IP3= inositol triphosphate; DAG=
THE ROLE OF NITRIC OXIDE DURING CEREBRAL
ISCHEMIA
ISCHEMIA

Minutes Hours / days

cNOS glutamate receptor


* *
L-Arginine L-citrulline + NO iNOS

GTP cGMP NO + superoxi

peroxynitrite

VASODILATATION CYTOTOXIC
cNOS = constitutive nitric oxide synthase iNOS = inducible nitric oxide synthase
NO = nitric oxide * inhibitors of NO synthase
GTP = guanosine triphosphate LNMMA = NG-monomethyl L-arginine
cGMP= cyclic guanosine monophosphate L-NNA = NG-nitro L-arginine
L-NAME = NG-nitroL-arginine-methyl ester
STROKE

(migration)

(adhesion)

INFLAMMATION AND FREE RADICALS


Stroke leucocytes activated inflammation migration +
adhesion of leucocytes.
Stroke leucocytes activated ROS + proteases + cytokines
GLUTAMATE AS A MAJOR ROLE IN ISCHEMIC STROKE
1
Timing of Inflammation
timing for the release
of mediators, as based
on animal models of
acute inflammation
vasoactive amines and
lipid mediators
promote exudation
and edema

followed by the expression of cytokines and chemokines that


activate the endothelium and mediate leukocyte migration
finally, anti-inflammatory mediators attenuate cell migration
and promote the apoptosis and clearance of leukocytes from
the inflammatory site.
The Onset of Inflammation
there are always some phagocytic cells in the tissue at all times
upon tissue injury or infection, these cells become active(e.g. ischemic stroke)
continue digesting foreign Ag and necrotic cells; secrete CYTOKINES
Enter the Conductor of Inflammation
Many classes of molecules
each with unique sources,
targets and effects

1
2

4
3 6
(TGF = transforming growth factor)
5
7
(ADHESION-STRENG-
THENING STAGE)

(SELECTIN-MEDIATED
ROLLING) (CRAWLING OF THE
GRANULOCYTE

LEUCOCYTE-ENDOTHELIUM INTERACTION
Vascular Response to Inflammation
Decreased blood flow allows
leukocytes to interact with
endothelium
rolling adhesion (weak) initiated via
interactions between carbohydrate
moieties and Selectins (stage I)
allows for strong interaction
between LFAs (leucocyte factor of
adhesion) and ICAMs (stage II) (Stage I)
(Stage II)
(Stage III)
rolling arrested and extravasation
begins (stage III)
MMPs (metalloproteinase) are
secreted to facilitate transversion of
the basement membrane
CASCADE OF APOPTOTIC EVENTS IN ISCHEMIA
(SCHULTZ 1999)
Lacunar
SMALL VESSEL DISEASE

Result from:

obstruction, which hinders the flow of blood


disorders of the muscles in the artery walls, causing
them to either constrict os dilate
aneurysms, which are weakened vessel segment thet
fill with blood and ballon outward
SMALL VESSEL DISEASE

Characterized by:
A thickening of the basement membrane
Proliferation of the endothelium
The development of microatheroma with a high content
of foam cells
The lacunar hypothesis proposes that (1) symptomatic lacunes
present with distinctive lacunar syndromes and (2) a lacune is due to
occlusion of a single deep penetrating artery generated by a specific
vascular pathology.

Lacunes may be defined as small subcortical infarcts (<15 mm in


diameter) in the territory of the deep penetrating arteries and may
present with specific lacunar syndromes or may be asymptomatic.

Lacunes occur most frequently in the basal ganglia and internal


capsule, thalamus, corona radiata, and pons.

Lacunar Stroke, www.emedicne.com


Pathophysiology:
Lacunes are caused by occlusion of a single penetrating artery. The
deep penetrating arteries are small nonbranching end arteries (usually
smaller than 500 mm in diameter), which arise directly from much
larger arteries (eg, the middle cerebral artery, anterior choroidal
artery, anterior cerebral artery, posterior cerebral artery, posterior
communicating artery, cerebellar arteries, basilar artery). Their small
size and proximal position predispose them to the development of
microatheroma and lipohyalinosis.

Initially, lipohyalinosis was thought to be the predominant small


vessel pathology of lacunes; however, microatheroma now is thought to
be the most common mechanism of arterial occlusion (or stenosis).

Lacunar Stroke, www.emedicne.com


Occasionally, atheroma in the parent artery blocks the orifice
of the penetrating artery (luminal atheroma), or atheroma involves
the origin of the penetrating artery (junctional atheroma).

A hemodynamic (hypoperfusion) mechanism is suggested when


there is a stenosis (and not occlusion) of the penetrating artery.

When no evidence of small vessel disease is found on histologic


examination, an embolic cause is assumed, either artery-to-artery
embolism or cardioembolism. In one recent series, 25% of patients
with clinical radiologically defined lacunes had a potential cardiac
cause for their strokes

Lacunar Stroke, www.emedicne.com


Symptoms
Each of the 5 classical lacunar syndromes has a symptom complex that
is relatively specific to it. Occasionally, cortical infarcts and
intracranial hemorrhages can mimic a lacunar syndrome. Cortical
symptoms (eg, aphasia, neglect) and visual field defects are absent.

Pure motor stroke/hemiparesis


This is the most common (33-50%) lacunar syndrome. It consists
of hemiparesis or hemiplegia that typically affects the face, arm,
and leg equally; The lacune is usually in the posterior limb of the
internal capsule or the basis pontis.

Ataxic hemiparesis
This is the second most frequent lacunar syndrome, consisting of
weakness and clumsiness on one side of the body.
The most frequent sites of infarction are the posterior limb of
the internal capsule, basis pontis, and corona radiata.

Lacunar Stroke, www.emedicne.com


Dysarthria/clumsy hand
The main symptoms are dysarthria and clumsiness (ie, weakness)
of the hand, which often is most prominent when the patient is
writing.

Pure sensory stroke


This lacunar syndrome consists of persistent or transient
numbness and/or tingling on one side of the body (eg, face, arm,
leg, trunk).
Occasionally, the complaint is of pain, burning, or other
unpleasant sensation. The infarct is usually in the thalamus.

Mixed sensorimotor stroke


With this lacunar syndrome, hemiparesis or hemiplegia is noted
with ipsilateral sensory impairment.
The infarct is usually in the thalamus and adjacent posterior
internal capsule (seemingly, in both the carotid and
vertebrobasilar territories).
Lacunar Stroke, www.emedicne.com