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Table of Contents
Year : 2022  |  Volume : 13  |  Issue : 4  |  Page : 265-266

Cerebral edema: Role of insulin and insulin signaling pathways in the brain

1 Department of Critical Care Medicine, Physician Regional Medical Center, Naples, FL, USA
2 Department of Research, Colombian Clinical Research Group in Neurocritical Care, Bogota, Colombia

Date of Submission16-Jun-2022
Date of Acceptance25-Jun-2022
Date of Web Publication31-Oct-2022

Correspondence Address:
Dr. Luis Rafael Moscote-Salazar
Colombian Clinical Research Group in Neurocritical Care, Bogota
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injms.injms_73_22

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How to cite this article:
Janjua T, Moscote-Salazar LR. Cerebral edema: Role of insulin and insulin signaling pathways in the brain. Indian J Med Spec 2022;13:265-6

How to cite this URL:
Janjua T, Moscote-Salazar LR. Cerebral edema: Role of insulin and insulin signaling pathways in the brain. Indian J Med Spec [serial online] 2022 [cited 2023 Jun 7];13:265-6. Available from: http://www.ijms.in/text.asp?2022/13/4/265/360048

Dear Editor,

Cerebral edema is defined as the increase in the net content of water at the cerebral level that leads to an increase in the volume of the brain tissue.[1] In the progression from the initial injury and with the subsequent development of cerebral edema, complex mechanisms have been linked at the cellular, structural, and microcirculation levels. Intracranial hypertension is one of the situations that occur with the worsening of cerebral edema.

Insulin has some interesting functions at the level of the mammalian brain; the receptor for insulin is distributed in the synaptic endings. The specific areas in the animal model are shown to be in the external median eminence and the hypothalamic arcuate nucleus.[2] Insulin crosses the blood–brain barrier through an insulin receptor-specific and vesicle-mediated process across brain endothelial cells.[3] There is more to central insulin besides control of food intake, central response to hypoglycemia, and impact of hyperglycemia/hypoglycemia-induced cerebral changes. Insulin-like growth factor 1 impacts acute brain injury in vitro with a reduction in brain cells' water content, infarct volume reduction, and reduced apoptosis.[4] An experimental model shows that pretreatment with insulin-like peptide 1 reduces oxidative stress, blood–brain barrier breakdown, cerebral edema formation, and cell injury.[5] Intranasal insulin can act as a neuroprotective agent in Alzheimer's disease[6] and acute ischemic stroke.[7] In vitro model, intranasal insulin significantly reduced hematoma volume and brain edema after induced cerebral hemorrhage. Also was seen decreased blood–brain barrier permeability, neuronal degeneration damage, reduced neurobehavioral deficits, and improved survival rate in mice.[8] Insulin reduced the lactate/pyruvate ratio and increased interstitial fluid glucose levels in subarachnoid hemorrhage in vitro. Other changes seen were improved neurological dysfunction, blood–brain barrier damage, and brain edema.[9]

The same effect can be inferred in the case of traumatic brain injury (TBI)-induced cerebral edema. Further work will be required in human trials to see the impact and any true benefit in preventing cerebral edema. The question is still there if the blood glucose control protocol used with insulin therapy in neurointensive care and trauma units has any impact on TBI-induced cerebral edema. Hypoglycemic episodes with this protocol can mitigate any impact of this approach.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Zusman BE, Kochanek PM, Jha RM. Cerebral edema in traumatic brain injury: A historical framework for current therapy. Curr Treat Options Neurol 2020;22:9.  Back to cited text no. 1
van Houten M, Posner BI, Kopriwa BM, Brawer JR. Insulin binding sites localized to nerve terminals in rat median eminence and arcuate nucleus. Science 1980;207:1081-3.  Back to cited text no. 2
Gray SM, Aylor KW, Barrett EJ. Unravelling the regulation of insulin transport across the brain endothelial cell. Diabetologia 2017;60:1512-21.  Back to cited text no. 3
Gong P, Zou Y, Zhang W, Tian Q, Han S, Xu Z, et al. The neuroprotective effects of Insulin-Like Growth Factor 1 via the Hippo/YAP signaling pathway are mediated by the PI3K/AKT cascade following cerebral ischemia/reperfusion injury. Brain Res Bull 2021;177:373-87.  Back to cited text no. 4
Sharma HS, Lafuente JV, Muresanu DF, Sahib S, Tian ZR, Menon PK, et al. Neuroprotective effects of insulin like growth factor-1 on engineered metal nanoparticles Ag, Cu and Al induced blood-brain barrier breakdown, edema formation, oxidative stress, upregulation of neuronal nitric oxide synthase and brain pathology. Prog Brain Res 2021;266:97-121.  Back to cited text no. 5
Yang JJ. Brain insulin resistance and the therapeutic value of insulin and insulin-sensitizing drugs in Alzheimer's disease neuropathology. Acta Neurol Belg 2022. [doi: 10.1007/s13760-022-01907-2].  Back to cited text no. 6
Lioutas VA, Alfaro-Martinez F, Bedoya F, Chung CC, Pimentel DA, Novak V. Intranasal insulin and insulin-like growth factor 1 as neuroprotectants in acute ischemic stroke. Transl Stroke Res 2015;6:264-75.  Back to cited text no. 7
Zhu Y, Huang Y, Yang J, Tu R, Zhang X, He WW, et al. Intranasal insulin ameliorates neurological impairment after intracerebral hemorrhage in mice. Neural Regen Res 2022;17:210-6.  Back to cited text no. 8
[PUBMED]  [Full text]  
Xu LB, Huang HD, Zhao M, Zhu GC, Xu Z. Intranasal insulin treatment attenuates metabolic distress and early brain injury after subarachnoid hemorrhage in mice. Neurocrit Care 2021;34:154-66.  Back to cited text no. 9


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