Table 3.

Effect of plasminogen activator application to cells of the CNS in culture or infusion into subjects in the setting of MCA occlusion

PA	Dose range	Target	Strain	MMP-2	MMP-9	MMP-3	References
Administration of exogenous PA, in vitro
rt-PA	5 μg/mL	Astrocyte	Rat Sprague–Dawley	↑	↑		254
rt-PA	1–10 μg/mL	Astrocyte	Rat Sprague–Dawley	↑	↑		181
u-PA	10–250 μg/mL			↑	↑
rt-PA	1–20 μg/mL (10 μg/mL)	Endothelial cell	Human (commercial)	↑	↑		179
rt-PA	5–30 μg/mL	Endothelial cell	Mouse bEnd.3			↑	180
Administration of exogenous PA, in vivo
rt-PA	10 mg/kg, IV	Transient MCA occlusion (embolic)	SHR	~	↑ or ~a		254
rt-PA	10 mg/kg, IV	Transient focal ischemia (intraluminal)	SHR	~	↑		174
Deficit in endogenous t-PA
t-PA−/−	–	Permanent MCA occlusion (intraluminal)	C57BL/6		↓		179
t-PA−/−	–	Transient focal ischemia (intraluminal)	C57BL/6		↓		174
	rt-PA 10 mg/kg, IV				↑

Abbreviations: CNS, central nervous system; MCA, middle cerebral artery; MMP, matrix metalloproteinase; PA, plasminogen activator; rt-PA, recombinant tissue plasminogen activator; t-PA, tissue-type plasminogen activator; SHR, spontaneously hypertensive rat; IV, intravenous.

^aIncrease noted only at 12 hours after ischemia, no difference at 24 hours.

Note: ↑ indicates increase; ↓, decrease; and ~, no change or no effect.