US 11,998,001 B2
Perfusion device for normothermic, ex vivo preservation of a mammalian brain
Stefano Daniele, New Haven, CT (US); Nenad Sestan, Madison, CT (US); John Silbereis, Hamden, CT (US); and Zvonimir Vrselja, New Haven, CT (US)
Assigned to Yale University, New Haven, CT (US)
Appl. No. 16/967,925
Filed by YALE UNIVERSITY, New Haven, CT (US)
PCT Filed Feb. 8, 2019, PCT No. PCT/US2019/017206
§ 371(c)(1), (2) Date Aug. 6, 2020,
PCT Pub. No. WO2019/157277, PCT Pub. Date Aug. 15, 2019.
Claims priority of provisional application 62/628,621, filed on Feb. 9, 2018.
Prior Publication US 2021/0360913 A1, Nov. 25, 2021
Int. Cl. A01N 1/02 (2006.01)
CPC A01N 1/021 (2013.01) 23 Claims
 
1. A perfusion device for the normothermic, ex vivo preservation of a mammalian brain, the device comprising:
a perfusion loop comprising a filtration loop having at least one hemodiafiltration unit adapted and configured to remove metabolic toxins from and add nutrients to a perfusate; and
a controller programmed to regulate at least a perfusate temperature within the perfusion loop to maintain normothermic conditions; and
a brain enclosure unit adapted and configured to receive and house a mammalian brain; and
a heat exchange unit adapted and configured to regulate the temperature of the brain enclosure unit and the perfusion loop;
wherein the perfusion loop is adapted and configured to oxygenate/carboxygenate the perfusate and circulate the perfusate through the brain contained within the brain enclosure unit; and
wherein, the perfusate comprises:
a culture medium comprising glucose, one or more amino acids, one or more water soluble salts and one more vitamins;
one or more artificial oxygen carrier compounds; and
one or more compounds selected from the group consisting of anti-cytotoxic compounds, antioxidants, anti-necrotic compounds, antiexcitotoxic compounds, anti-inflammatory compounds, antiepileptic compounds, anti-apoptotic compounds, antibiotics, cell death inhibitors, neuroprotectants and oxidative/nitrosative stress inhibitors.