Table 1.

Laboratory studies of antioxidant and anti-inflammatory combination therapies with rt-PA.

Therapy (Author / Year)	Animal Model	Therapeutic Target	Treatment	Outcomes
Minocycline (Fan et al. 2013)¹⁰	Thromboembolic stroke, rat	p38 MAPK	rt-PA alone (1.5h post emboliztion) vs rt-PA + minocycline 1h, post embolization)	Minocycline ↓ infarct volume, hemorrhage, & edema
BB-94 (Lapchak et al. 2000)¹¹	Large clot embolic Stroke, rabbit	MMPs	rt-PA (1h post embolization) vs. rt-PA + BB-94 5 min after embolization.	BB-94 ↓rt-PA-induced hemorrhage
EGCG (You et al. 2016)¹²	Thromboembolic stroke, rat	MMPs, ROS	EGCG every 4h after embolization treated + rt-PA	EGCG ↓rt-PA extended therapeutic window, ↓ infarct volume, edema, & BBB disruption
Progranulin (Kanazawa et al. 2015)¹³	Thromboembolic stroke, rat	inflammation	rt-PA (4h post MCAO), vs. PA +progranulin immediately before rt-PA rt-	Progranulin ↓infarct size, cerebral edema, rt-PA induced hemorrhagic transformation; improved motor outcome
G-CSF (dela Peña et al. 2015)¹⁴	tMCAO x 1 h, rat	IL-1β, iNOS, apoptosis	IV rt-PA vs. rt-PA + G-CSF immediately before reperfusion	rt-PA+G-CSF ↓neurological deficit & hemorhhagic transformation vs rt-PA alone
NXY-059G (Lapchak et al. 2002)¹⁵	Large clot embolic Stroke rabbit	ROS	NXY-059G 5min after embolization vs. rt-PA 1h after embolization + NXY-059G	NXY-059G + rt-PA ↓ rt-PA-induced hemorrhagic transformation and ↑behavioral function.
Uric Acid (Romanos et al. 2007)¹⁶	Thromboembolic stroke, rat	ROS	rt-PA + uric acid 20 mins after occlusion	Uric acid+rt-PA ↓infarct volume, ↑neurological function
Edaravone (Yagi et al. 2009)¹⁷	tMCAO x 3h, rat	ROS and MMP-9	rt-PA alone vs rt-PA + edaravone immediately after reperfusion	Edaravone ↓ rt-PA-induced hemorrhagic transformation
Hypothermia (Tang et al. 2013)¹⁸	tMCAO x 1 or 3 h, rat	multiple mechanisms	rt-PA 1h or 3h after ischemia vs. rt-PA plus cooling (33 °C) prior to or concurrent with rt-PA	hypothermia ↓infarct size, neurological deficits, brain hemorrhage, BBB disruption

Abbreviations: rt-PA=recombinant tissue plasminogen activator; MMP=matrix metalloproteinase; tMCAO=transient middle cerebral artery occlusion; EGCG=epigallocatechin gallate; ROS=reactive oxygen species; BBB=blood brain barrier; G-CSF=granulocyte-colony stimulating factor; iNOS=inducible nitric oxide synthase;