title: Infusion of human embryonic kidney cell line conditioned medium reverses kainic acid induced hippocampal damage in mice.
abstract: OBJECTIVE
  Hippocampal neurodegeneration is one of the hallmarks in neurological and neurodegenerative diseases such as temporal lobe epilepsy and Alzheimer disease. Human embryonic kidney (HEK) cells are a mixed population of cells, including neurons, and their conditioned medium is enriched with erythropoietin (EPO). Because EPO is a known neuroprotectant, we hypothesized that infusion of HEK cells or HEK-conditioned medium (HEK-CM) may provide neuroprotection against kainic acid (KA)-induced hippocampal damage in mice.
  
  
  METHODS
  Adult CF1 mice were treated with KA to induce hippocampal damage. On 3rd and 5th days after KA treatment, HEK cells or HEK-CM was infused intravenously through the tail vein. On the 7th and 8th days after KA treatment, all groups of mice were subjected to cognitive and depression assessment by use of a novel object recognition test and a forced swim test, respectively. Subsequent to this assessment, mice were killed and the brain samples were used to assess the histopathology and messenger RNA expression for EPO and B-cell lymphoma-2 (Bcl-2).
  
  
  RESULTS
  We found that infusion of HEK cells/HEK-CM improves cognitive function and alleviates symptoms of depression. Histological assessment demonstrates complete neuroprotection against KA-mediated excitotoxicity, and the hippocampal cytoarchitecture of HEK cells/HEK-CM treated mice was comparable to normal control mice. HEK cells/HEK-CM treatment could provide neuroprotection by upregulating the endogenous EPO and Bcl-2 in KA-treated mice.
  
  
  CONCLUSIONS
  Our present data demonstrate for the first time that infusion of HEK cells/HEK-CM can prevent excitotoxic hippocampal damage and alleviate consequent behavioral abnormalities.
authors.affiliation: School of Regenerative Medicine, Manipal University, Yelahanka, Bangalore, India.
authors.forename: Anandh
authors.initials: A
authors.lastname: Dhanushkodi
authors.affiliation: School of Regenerative Medicine, Manipal University, Yelahanka, Bangalore, India.
authors.forename: Chaitra
authors.initials: C
authors.lastname: Venugopal
authors.affiliation: School of Regenerative Medicine, Manipal University, Yelahanka, Bangalore, India.
authors.forename: Pradeep Kumar K
authors.initials: PK
authors.lastname: Bevinahal
authors.affiliation: Department of Physiology, Melaka Manipal Medical College, Manipal University, Manipal, India.
authors.forename: Kiranmai S
authors.initials: KS
authors.lastname: Rai
authors.affiliation: National Institute of Mental Health and Neurosciences, Deemed University, Bangalore, 29, India.
authors.forename: Raju R
authors.initials: RR
authors.lastname: Trichur
authors.affiliation: National Institute of Mental Health and Neurosciences, Deemed University, Bangalore, 29, India.
authors.forename: Sathyaprabha N
authors.initials: SN
authors.lastname: Talakad
authors.affiliation: School of Regenerative Medicine, Manipal University, Yelahanka, Bangalore, India. Electronic address: rr.bhonde@manipal.edu.
authors.forename: Ramesh R
authors.initials: RR
authors.lastname: Bhonde
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000009:adverse effects* / Q000494:pharmacology; D057809:HEK293 Cells; D006624:Hippocampus / Q000293:injuries* / Q000378:metabolism; D006801:Humans; D007608:Kainic Acid / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D051379:Mice; D013997:Time Factors
chemical_list: D017077:Culture Media, Conditioned; D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid
keywords: HEK cells; conditioned medium; hippocampus; kainic acid; neurodegeneration; neuroprotection