Homocysteine decreases blood flow to the brain due to vascular resistance in carotid artery

Munish Kumar, Neetu Tyagi, Karni S. Moshal, Utpal Sen, Soumi Kundu, Paras Kumar Mishra, Srikanth Givvimani, Suresh C. Tyagi

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

An elevated level of Homocysteine (Hcy) is a risk factor for vascular dementia and stroke. Cysthathionine β Synthase (CBS) gene is involved in the clearance of Hcy. Homozygous individuals for (CBS-/-) die early, but heterozygous for (CBS-/+) survive with high levels of Hcy. The γ-Amino Butyric Acid (GABA) presents in the central nervous system (CNS) and functions as an inhibitory neurotransmitter. Hcy competes with GABA at the GABAA receptor and affects the CNS function. We hypothesize that Hcy causes a decrease in blood flow to the brain due to increase in vascular resistance (VR) because of arterial remodeling in the carotid artery (CA). Blood pressure and blood flow in CA of wild type (WT), CBS-/+, CBS-/+ GABAA-/- double knockout, and GABAA-/- were measured. CA was stained with trichrome, and the brain permeability was measured. Matrix Metalloproteinases (MMP-2 and MMP-9), tissue inhibitor of metalloproteinase (TIMP-3, TIMP-4), elastin, and collagen-III expression were measured by real-time polymerase chain reaction (RT-PCR). Results showed an increase in VR in CBS-/+/GABAA-/-double knockout > CBS-/+/ > GABAA-/- compared to WT mice. Increased MMP-2, MMP-9, collagen-III and TIMP-3 mRNA levels were found in GABAA-/-, CBS-/+, CBS-/+/GABAA double knockout compared to WT. The levels of TIMP-4 and elastin were decreased, whereas the levels of MMP-2, MMP-9 and TIMP-3 increased, which indirectly reflected the arterial resistance. These results suggested that Hcy caused arterial remodeling in part, by increase in collagen/elastin ratio thereby increasing VR leading to the decrease in CA blood flow.

Original languageEnglish (US)
Pages (from-to)214-219
Number of pages6
JournalNeurochemistry International
Volume53
Issue number6-8
DOIs
StatePublished - Dec 1 2008
Externally publishedYes

Fingerprint

Homocysteine
Matrix Metalloproteinases
Carotid Arteries
Tissue Inhibitor of Metalloproteinase-3
Vascular Resistance
Elastin
Brain
Collagen
gamma-Aminobutyric Acid
Central Nervous System
Vascular Dementia
Butyric Acid
Matrix Metalloproteinase 2
GABA-A Receptors
Neurotransmitter Agents
Real-Time Polymerase Chain Reaction
Permeability
Stroke
Blood Pressure
Messenger RNA

Keywords

  • Carotid artery
  • Edema
  • MMP
  • Vascular resistance

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Homocysteine decreases blood flow to the brain due to vascular resistance in carotid artery. / Kumar, Munish; Tyagi, Neetu; Moshal, Karni S.; Sen, Utpal; Kundu, Soumi; Mishra, Paras Kumar; Givvimani, Srikanth; Tyagi, Suresh C.

In: Neurochemistry International, Vol. 53, No. 6-8, 01.12.2008, p. 214-219.

Research output: Contribution to journalArticle

Kumar, M, Tyagi, N, Moshal, KS, Sen, U, Kundu, S, Mishra, PK, Givvimani, S & Tyagi, SC 2008, 'Homocysteine decreases blood flow to the brain due to vascular resistance in carotid artery', Neurochemistry International, vol. 53, no. 6-8, pp. 214-219. https://doi.org/10.1016/j.neuint.2008.07.008
Kumar, Munish ; Tyagi, Neetu ; Moshal, Karni S. ; Sen, Utpal ; Kundu, Soumi ; Mishra, Paras Kumar ; Givvimani, Srikanth ; Tyagi, Suresh C. / Homocysteine decreases blood flow to the brain due to vascular resistance in carotid artery. In: Neurochemistry International. 2008 ; Vol. 53, No. 6-8. pp. 214-219.
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