@ARTICLE{Benardete2002-kl,
  title    = "Increased excitability and decreased sensitivity to {GABA} in an
              animal model of dysplastic cortex",
  author   = "Benardete, Ethan A and Kriegstein, Arnold R",
  abstract = "PURPOSE: Cortical dysplasia (CD) is associated with epilepsy in
              both the pediatric and adult populations. The mechanism
              underlying seizures with cortical malformations is still poorly
              understood. To study the physiology of dysplastic cortex, we
              developed an experimental model of CD. METHODS: Pregnant rats
              were given intraperitoneal injections of carmustine
              (1-3-bis-chloroethyl-nitrosourea; BCNU) on embryonic day 15
              (E15). Cortical histology was examined in the resulting pups at
              P0, P28, and P60. In addition, evoked and spontaneous field
              potential recordings were obtained in cortical slices from adult
              control and BCNU-exposed rats. Finally, we used whole-cell
              recordings to compare physiologic properties of pyramidal neurons
              and gamma-aminobutyric acid (GABA) responses in control and
              BCNU-treated animals. RESULTS: Features characteristic of CD were
              found in the offspring, including laminar disorganization,
              cytomegalic neurons, and neuronal heterotopias. Dysplastic cortex
              also contained abnormal clusters of Cajal-Retzius (CR) cells and
              disruption of radial glial fibers, as demonstrated with
              immunohistochemistry. Under conditions of partial GABAA-receptor
              blockade with 10 microM bicuculline methiodide (BMI), slices of
              dysplastic cortex demonstrated a significant increase in the
              number of spontaneous and evoked epileptiform discharges.
              Individual pyramidal neurons in dysplastic cortex were less
              sensitive to application of GABA compared with controls.
              CONCLUSIONS: BCNU exposure in utero produces histologic
              alterations suggestive of CD in rat offspring. Dysplastic cortex
              from this model demonstrates features of hyperexcitability and
              decreased neuronal sensitivity to GABA. Such physiologic
              alterations may underlie the increased epileptogenicity of
              dysplastic cortex.",
  journal  = "Epilepsia",
  volume   =  43,
  number   =  9,
  pages    = "970--982",
  month    =  sep,
  year     =  2002,
  address  = "United States",
  language = "en"
}

{"_id":"NccSXTd2sudxorcAi","bibbaseid":"benardete-kriegstein-increasedexcitabilityanddecreasedsensitivitytogabainananimalmodelofdysplasticcortex-2002","author_short":["Benardete, E. A","Kriegstein, A. R"],"bibdata":{"bibtype":"article","type":"article","title":"Increased excitability and decreased sensitivity to GABA in an animal model of dysplastic cortex","author":[{"propositions":[],"lastnames":["Benardete"],"firstnames":["Ethan","A"],"suffixes":[]},{"propositions":[],"lastnames":["Kriegstein"],"firstnames":["Arnold","R"],"suffixes":[]}],"abstract":"PURPOSE: Cortical dysplasia (CD) is associated with epilepsy in both the pediatric and adult populations. The mechanism underlying seizures with cortical malformations is still poorly understood. To study the physiology of dysplastic cortex, we developed an experimental model of CD. METHODS: Pregnant rats were given intraperitoneal injections of carmustine (1-3-bis-chloroethyl-nitrosourea; BCNU) on embryonic day 15 (E15). Cortical histology was examined in the resulting pups at P0, P28, and P60. In addition, evoked and spontaneous field potential recordings were obtained in cortical slices from adult control and BCNU-exposed rats. Finally, we used whole-cell recordings to compare physiologic properties of pyramidal neurons and gamma-aminobutyric acid (GABA) responses in control and BCNU-treated animals. RESULTS: Features characteristic of CD were found in the offspring, including laminar disorganization, cytomegalic neurons, and neuronal heterotopias. Dysplastic cortex also contained abnormal clusters of Cajal-Retzius (CR) cells and disruption of radial glial fibers, as demonstrated with immunohistochemistry. Under conditions of partial GABAA-receptor blockade with 10 microM bicuculline methiodide (BMI), slices of dysplastic cortex demonstrated a significant increase in the number of spontaneous and evoked epileptiform discharges. Individual pyramidal neurons in dysplastic cortex were less sensitive to application of GABA compared with controls. CONCLUSIONS: BCNU exposure in utero produces histologic alterations suggestive of CD in rat offspring. Dysplastic cortex from this model demonstrates features of hyperexcitability and decreased neuronal sensitivity to GABA. Such physiologic alterations may underlie the increased epileptogenicity of dysplastic cortex.","journal":"Epilepsia","volume":"43","number":"9","pages":"970–982","month":"September","year":"2002","address":"United States","language":"en","bibtex":"@ARTICLE{Benardete2002-kl,\n title = \"Increased excitability and decreased sensitivity to {GABA} in an\n animal model of dysplastic cortex\",\n author = \"Benardete, Ethan A and Kriegstein, Arnold R\",\n abstract = \"PURPOSE: Cortical dysplasia (CD) is associated with epilepsy in\n both the pediatric and adult populations. The mechanism\n underlying seizures with cortical malformations is still poorly\n understood. To study the physiology of dysplastic cortex, we\n developed an experimental model of CD. METHODS: Pregnant rats\n were given intraperitoneal injections of carmustine\n (1-3-bis-chloroethyl-nitrosourea; BCNU) on embryonic day 15\n (E15). Cortical histology was examined in the resulting pups at\n P0, P28, and P60. In addition, evoked and spontaneous field\n potential recordings were obtained in cortical slices from adult\n control and BCNU-exposed rats. Finally, we used whole-cell\n recordings to compare physiologic properties of pyramidal neurons\n and gamma-aminobutyric acid (GABA) responses in control and\n BCNU-treated animals. RESULTS: Features characteristic of CD were\n found in the offspring, including laminar disorganization,\n cytomegalic neurons, and neuronal heterotopias. Dysplastic cortex\n also contained abnormal clusters of Cajal-Retzius (CR) cells and\n disruption of radial glial fibers, as demonstrated with\n immunohistochemistry. Under conditions of partial GABAA-receptor\n blockade with 10 microM bicuculline methiodide (BMI), slices of\n dysplastic cortex demonstrated a significant increase in the\n number of spontaneous and evoked epileptiform discharges.\n Individual pyramidal neurons in dysplastic cortex were less\n sensitive to application of GABA compared with controls.\n CONCLUSIONS: BCNU exposure in utero produces histologic\n alterations suggestive of CD in rat offspring. Dysplastic cortex\n from this model demonstrates features of hyperexcitability and\n decreased neuronal sensitivity to GABA. Such physiologic\n alterations may underlie the increased epileptogenicity of\n dysplastic cortex.\",\n journal = \"Epilepsia\",\n volume = 43,\n number = 9,\n pages = \"970--982\",\n month = sep,\n year = 2002,\n address = \"United States\",\n language = \"en\"\n}\n\n","author_short":["Benardete, E. A","Kriegstein, A. R"],"key":"Benardete2002-kl","id":"Benardete2002-kl","bibbaseid":"benardete-kriegstein-increasedexcitabilityanddecreasedsensitivitytogabainananimalmodelofdysplasticcortex-2002","role":"author","urls":{},"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://bibbase.org/f/EJMp3HRuxirjxpcXh/references.bib","dataSources":["sAFYeB74DpbdXM9NN","4zx9n2tbeLTix3Wxr","k3cdWrThyTh5o59Rm","hq9pebjzmsTuyxGGx","h8Atv2SAy4PmShg5j","vCGHbq7YMoL4xbgTv"],"keywords":[],"search_terms":["increased","excitability","decreased","sensitivity","gaba","animal","model","dysplastic","cortex","benardete","kriegstein"],"title":"Increased excitability and decreased sensitivity to GABA in an animal model of dysplastic cortex","year":2002}