TABLE 1.

Researches related to the blood-brain barrier dysfunction after burn injury.

Author	Research subjects	Burn model	Concerns	Results
Barone et al., 1997	Adult Sprague-Dawley rats	A third degree burn affecting 70% TBSA	The albumin leak in the cerebral vessels	Thermal injury led to an increased permeability of cerebral vessels.
Randolph et al., 2019	Female merino sheep	A third degree burn affecting 40% TBSA combined with smoke inhalation	BBB integrity and hemorrhage	Third-degree skin burn injury combined with smoke inhalation produced massive cerebral hemorrhaging, and BBB dysfunction characterized by congested and dilated blood vessels, as well as neutrophil infiltration into the brain.
Berger et al., 2007.	Adult Sprague-Dawley rats	A third degree burn affecting 70% TBSA	BBB integrity, brain edema, and MMP levels in the brain	The significant increase in cerebral permeability after serious systemic thermal injury could be related to early expression of MMPs.
Swann et al., 2007.	Adult Sprague-Dawley rats	A third degree burn affecting 60–70% TBSA	Brain edema and MMPs levels	The increase in MMP-9 expression and activity, associated with increased BBB permeability following thermal injury, indicates that MMP-9 may contribute to observed cerebral edema in peripheral thermal injury.
Li et al., 2009	Male mongrel dogs	A third degree burn affecting 50% TBSA	The manifestation of MRI and histopathology; changes of brain water content; the shapes and distribution of the cerebral capillaries; the volume, surface, and length fractions of cerebral capillaries	The changes of cerebral blood flow might play an important role in the pathogenesis of brain edema in the early stage of severe burn.
Patel et al., 2008	Adult male Sprague–Dawley rats	A third degree burn affecting 60–70% TBSA	BBB dysfunction; levels of tPA and uPA in the brain	Peripheral thermal injury induced an increase in the permeability of the BBB, which may be related with the increased expression of tPA and uPA,
Liu et al., 2009	Adult male Sprague–Dawley rats	A third degree burn affecting 30% TBSA	BBB permeability; brain edema; GFAP expression in the brain	The increase in GFAP expression may be associated with the increased BBB permeability following thermal injury.
Liu et al., 2011	Adult male Sprague–Dawley rats	A third degree burn affecting 30% TBSA	BBB permeability; the expression levels of ZO-1	The increased permeability of BBB after severe burns in the rat model may be related to the decreased expression of ZO-1.
Wang and Yang, 2005	Adult male Sprague–Dawley rats	A third degree burn affecting 40% TBSA	BBB permeability and brain edema	Burn injury induced an increase in the permeability of the BBB, leading to brain edema.
Moati et al., 1979	Burn injured patients; Rats	A third degree burn affecting 30% TBSA	BBB permeability	BBB permeabilizing activity was related to collagenolytic activity.
Yang et al., 2020	Wild-type C57BL/6J female mice	A third degree burn affecting 30% TBSA	Transcellular vesicular transport (transcytosis) in BBB; neuroinflammtion; tight junction proteins (TJs)	Burns could induce an increase in the permeability of BBB via paracellular pathway as well as transcytosis. Umbilical cord-derived mesenchymal stem cells could protect the integrity of BBB after burns by protecting the tight junction, as well as reducing transcytosis and neuroinflammation.
Reyes et al., 2009	Adult male Sprague–Dawley rats	A third degree burn affecting 70% TBSA	BBB permeability and neuroiflammation	The expression of TNF-α, IL-1β and ICAM-1 were elevated at 3 h and remained high at 7 h following burn injury.
Jiang et al., 2021	Adult male Sprague–Dawley rats	A third degree burn affecting 30% TBSA	Levels of HIF-1α, Claudin5, ZO-1, and VE-cadherin	Burn injury enhanced vascular permeability, resulting in the disruption of endothelial cell junction integrity.
Basch and Fazekas, 1970	Wistar rats	A third degree burn affecting 20% TBSA	BBB permeability	BBB permeability was considerably ruptured even 5 days after burn injury.
Khan et al., 2020	Male albino mice	A burn injury affecting 25% TBSA	Cognitive behaviors; the JNK/caspase-3 and BDNF/VEGF levels; pro-inflammatory cytokine; levels of antioxidant, nitric oxide, and corticosterone	The cognitive behavior defects after burn injury may be related with the modulation of JNK-mediated inflammation, oxidative stress, apoptosis, and BDNF/VEGF signaling in an acute mouse model with burn injury.
Cherry et al., 2013	C57BL/6J female mice	A full thickness burn affecting 10% TBSA combined whole-body gamma irradiation	Learning and memory capacity; vascular activation; neuroinflammation; neurogenesis	Thermal injury lowered the threshold for radiation-induced neuroinflammation and cognitive dysfunction.