Details of Disease

General Information of Disease (ID: DIS9Q4RT)

• Disease Name: Brain ischaemia
• Synonyms: ischemic disease of brain; brain ischemia; ischaemic disease of brain; ischemia cerebrovascular; ischemic encephalopathy; ischaemic encephalopathy; brain ischemic disease; cerebrovascular ischemia; brain ischaemic disease
• Disease Class: 8B1Z: Cerebral ischaemia
• Definition: Diminished or absent blood supply to the brain caused by obstruction (thrombosis or embolism) of an artery resulting in neurologic damage.
• Disease Hierarchy:
  DISAB237: Cerebrovascular disease
  DIS5XOOY: Ischemia
  DIS9Q4RT: Brain ischaemia
• ICD Code:
  ICD-11: ICD-11: 8B1Z
  ICD-10: ICD-10: I67.8
  ICD-9: ICD-9: 435, 437
  Expand ICD-11: '8B1Z
  Expand ICD-10: 'I67.8
  Expand ICD-9: 435437
• Disease Identifiers:
  MONDO ID: MONDO_0005299
  MESH ID: D002545
  UMLS CUI: C0917798
  MedGen ID: 182975
  HPO ID: HP:0002637
  SNOMED CT ID: 287731003

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 5 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Abciximab	DMJO6GV	Approved	Monoclonal antibody	[1]
Nicergoline	DMBCM8L	Approved	Small molecular drug	[2]
Papaverine	DMCA9QP	Approved	Small molecular drug	[3]
Pentobarbital	DMFNH7L	Approved	Small molecular drug	[4]
Phentolamine	DMXYJOB	Approved	Small molecular drug	[5]

This Disease is Treated as An Indication in 3 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
HYDAMTIQ	DMY5RDI	Investigative	NA	[6]
LAU-0901	DMMDZ4B	Investigative	NA	[7]
Thieno-phenanthridin-6-one	DMFDROW	Investigative	NA	[8]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 42 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CCL3	TT8I4WB	Limited	Biomarker	[9]
CEBPB	TTUI35N	Limited	Biomarker	[9]
EGR1	TTE8LGD	Limited	Biomarker	[9]
MAPK1	TT4TQBX	Limited	Biomarker	[10]
MAPK3	TT1MG9E	Limited	Biomarker	[10]
NFKB1	TTUIZKC	Limited	Therapeutic	[11]
NFKBIA	TTSHAEB	Limited	Biomarker	[11]
SELE	TT1PL7M	Limited	Biomarker	[9]
ASIC1	TTRJYB6	moderate	Biomarker	[12]
BBC3	TT7JUKC	moderate	Biomarker	[13]
BDNF	TTSMLOH	moderate	Biomarker	[14]
CASP3	TTPF2QI	moderate	Biomarker	[10]
CHRM1	TTZ9SOR	moderate	Biomarker	[15]
HIF1A	TTSN6QU	moderate	Biomarker	[16]
ICAM1	TTA1L39	moderate	Biomarker	[17]
JUN	TTS7IR5	moderate	Biomarker	[10]
MAP2K1	TTIDAPM	moderate	Biomarker	[10]
MPO	TTVCZPI	moderate	Biomarker	[17]
PLAT	TTXAGYU	moderate	Therapeutic	[18]
ALB	TTFNGC9	Strong	Therapeutic	[19]
CASP9	TTB6T7O	Strong	Biomarker	[20]
CAT	TTPS279	Strong	Biomarker	[21]
CCL11	TTCF05Y	Strong	Biomarker	[22]
CCL2	TTNAY0P	Strong	Biomarker	[9]
CCR4	TT7HQD0	Strong	Biomarker	[22]
CXCL10	TTQOVYA	Strong	Biomarker	[22]
DIABLO	TTN74LE	Strong	Biomarker	[20]
F2	TT6L509	Strong	Biomarker	[23]
F5	TT1O264	Strong	Biomarker	[23]
GPX1	TTYAHBP	Strong	Therapeutic	[24]
IL10RB	TTJTRMK	Strong	Biomarker	[22]
IL17A	TTG0MT6	Strong	Biomarker	[22]
IL18	TTRICUF	Strong	Biomarker	[22]
IL1A	TTPM6HI	Strong	Biomarker	[22]
IL1RN	TT6GSR3	Strong	Therapeutic	[25]
MTHFR	TTQWOU1	Strong	Biomarker	[23]
PARP1	TTVDSZ0	Strong	Biomarker	[26]
PLAU	TTGY7WI	Strong	Therapeutic	[27]
SOD1	TTP9K3Q	Strong	Therapeutic	[20]
TNFRSF1A	TTG043C	Strong	Biomarker	[22]
TNFRSF1B	TT63WSF	Strong	Biomarker	[22]
UCP2	TTSC2YM	Strong	Biomarker	[28]

This Disease Is Related to 9 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ADD3	OTDRSHAZ	Limited	Biomarker	[10]
RELA	OTUJP9CN	Limited	Therapeutic	[11]
DYNLL1	OTR69LHT	moderate	Biomarker	[29]
RB1	OT9VMY7B	moderate	Biomarker	[10]
ACE	OTDF1964	Strong	Biomarker	[23]
CCL4	OT6B8P25	Strong	Biomarker	[22]
CYCS	OTBFALJD	Strong	Biomarker	[20]
IL12RB1	OTM1IJO2	Strong	Biomarker	[22]
IL17RA	OTVVI8ER	Strong	Biomarker	[22]

References

• [1] Emergent carotid stenting and intra-arterial abciximab in acute ischemic stroke due to tandem occlusion. Br J Neurosurg. 2017 Oct;31(5):573-579.
• [2] Drug information of Nicergoline, 2008. eduDrugs.
• [3] Intra-Arterial Papaverine-Hydrochloride and Transluminal Balloon Angioplasty for Neurointerventional Management of Delayed-Onset Post-Aneurysmal Subarachnoid Hemorrhage Vasospasm. World Neurosurg. 2018 Nov;119:e301-e312.
• [4] Pentobarbital FDA Label
• [5] Phentolamine FDA Label
• [6] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2771).
• [7] Superior Neuroprotective Efficacy of LAU-0901, a Novel Platelet-Activating Factor Antagonist, in Experimental Stroke. Transl Stroke Res. 2012 Mar;3(1):154-63.
• [8] Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors. Nat Rev Drug Discov. 2005 May;4(5):421-40.
• [9] Peroxisome proliferator-activated receptor-gamma agonists induce neuroprotection following transient focal ischemia in normotensive, normoglycemic as well as hypertensive and type-2 diabetic rodents.J Neurochem. 2007 Apr;101(1):41-56. doi: 10.1111/j.1471-4159.2006.04376.x.
• [10] Tamoxifen neuroprotection in cerebral ischemia involves attenuation of kinase activation and superoxide production and potentiation of mitochondrial superoxide dismutase.Endocrinology. 2008 Jan;149(1):367-79. doi: 10.1210/en.2007-0899. Epub 2007 Sep 27.
• [11] The role of Akt signaling in oxidative stress mediates NF-kappaB activation in mild transient focal cerebral ischemia.J Cereb Blood Flow Metab. 2008 Dec;28(12):1917-26. doi: 10.1038/jcbfm.2008.80. Epub 2008 Jul 16.
• [12] Extracellular spermine exacerbates ischemic neuronal injury through sensitization of ASIC1a channels to extracellular acidosis.J Neurosci. 2011 Feb 9;31(6):2101-12. doi: 10.1523/JNEUROSCI.4351-10.2011.
• [13] Potential role of PUMA in delayed death of hippocampal CA1 neurons after transient global cerebral ischemia.Stroke. 2009 Feb;40(2):618-25. doi: 10.1161/STROKEAHA.108.524447. Epub 2008 Dec 18.
• [14] Progesterone, BDNF and neuroprotection in the injured CNS.Int J Neurosci. 2009;119(10):1718-40. doi: 10.1080/00207450903116430.
• [15] Benzamide protects delayed neuronal death and behavioural impairment in a mouse model of global cerebral ischemia.Behav Brain Res. 2008 Oct 10;192(2):178-84. doi: 10.1016/j.bbr.2008.03.043. Epub 2008 Apr 8.
• [16] Hyperglycemia-enhanced ischemic brain damage in mutant manganese SOD mice is associated with suppression of HIF-1alpha.Neurosci Lett. 2009 Jun 5;456(2):89-92. doi: 10.1016/j.neulet.2009.03.076. Epub 2009 Mar 28.
• [17] Inhibition of NADPH oxidase is neuroprotective after ischemia-reperfusion.J Cereb Blood Flow Metab. 2009 Jul;29(7):1262-72. doi: 10.1038/jcbfm.2009.47. Epub 2009 May 6.
• [18] Red blood cell-coupled tissue plasminogen activator prevents impairment of cerebral vasodilatory responses through inhibition of c-Jun-N-terminal kinase and potentiation of p38 mitogen-activated protein kinase after cerebral photothrombosis in the newborn pig.Pediatr Crit Care Med. 2011 Nov;12(6):e369-75. doi: 10.1097/PCC.0b013e3181fe40a7.
• [19] The ALIAS Pilot Trial: a dose-escalation and safety study of albumin therapy for acute ischemic stroke--II: neurologic outcome and efficacy analysis.Stroke. 2006 Aug;37(8):2107-14. doi: 10.1161/01.STR.0000231389.34701.b5. Epub 2006 Jun 29.
• [20] Overexpression of copper/zinc superoxide dismutase in transgenic rats protects vulnerable neurons against ischemic damage by blocking the mitochondrial pathway of caspase activation.J Neurosci. 2002 Jan 1;22(1):209-17. doi: 10.1523/JNEUROSCI.22-01-00209.2002.
• [21] Nimesulide prevents oxidative stress damage following transient forebrain ischemia in the rat hippocampus.Res Commun Mol Pathol Pharmacol. 2004;115-116:49-62.
• [22] Superoxide dismutase 1 overexpression reduces MCP-1 and MIP-1 alpha expression after transient focal cerebral ischemia.J Cereb Blood Flow Metab. 2005 Oct;25(10):1312-24. doi: 10.1038/sj.jcbfm.9600124.
• [23] Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls.Arch Neurol. 2004 Nov;61(11):1652-61. doi: 10.1001/archneur.61.11.1652.
• [24] Glutathione peroxidase inhibits cell death and glial activation following experimental stroke.Brain Res Mol Brain Res. 2002 Dec 30;109(1-2):34-44. doi: 10.1016/s0169-328x(02)00459-x.
• [25] Cortical protection by localized striatal injection of IL-1ra following cerebral ischemia in the rat.J Cereb Blood Flow Metab. 1997 Jun;17(6):597-604. doi: 10.1097/00004647-199706000-00001.
• [26] Spatial and functional relationship between poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in the brain.Neuroscience. 2007 Aug 10;148(1):198-211. doi: 10.1016/j.neuroscience.2007.04.062. Epub 2007 Jul 19.
• [27] Preliminary efficacy report of a novel thrombolytic agent for acute ischaemic stroke within a 5-hour window.CNS Drugs. 2007;21(11):937-46. doi: 10.2165/00023210-200721110-00005.
• [28] Effects of rosiglitazone on global ischemia-induced hippocampal injury and expression of mitochondrial uncoupling protein 2.Biochem Biophys Res Commun. 2006 Dec 8;351(1):198-203. doi: 10.1016/j.bbrc.2006.10.017. Epub 2006 Oct 11.
• [29] Induction of protein inhibitor of neuronal nitric oxide synthase/cytoplasmic dynein light chain following cerebral ischemia.Neuroscience. 1998 May;84(1):81-8. doi: 10.1016/s0306-4522(97)00479-x.