title: Dorsomedial/Perifornical hypothalamic stimulation increases intraocular pressure, intracranial pressure, and the translaminar pressure gradient.
abstract: OBJECTIVE
  Intraocular pressure (IOP) fluctuation has recently been identified as a risk factor for glaucoma progression. Further, decreases in intracranial pressure (ICP), with postulated increases in the translaminar pressure gradient across the lamina cribrosa, has been reported in glaucoma patients. We hypothesized that circadian fluctuations in IOP and the translaminar pressure gradient are influenced, at least in part, by central autonomic regulatory neurons within the dorsomedial and perifornical hypothalamus (DMH/PeF). This study examined whether site-directed chemical stimulation of DMH/PeF neurons evoked changes in IOP, ICP, and the translaminar pressure gradient.
  
  
  METHODS
  The GABA(A) receptor antagonist bicuculline methiodide (BMI) was stereotaxically microinjected into the DMH/PeF region of isoflurane-anesthetized male Sprague-Dawley rats (n = 19). The resulting peripheral cardiovascular (heart rate [HR] and mean arterial pressure [MAP]), IOP, and ICP effects were recorded and alterations in the translaminar pressure gradient calculated.
  
  
  RESULTS
  Chemical stimulation of DMH/PeF neurons evoked significant increases in HR (+69.3 ± 8.5 beats per minute); MAP (+22.9 ± 1.6 mm Hg); IOP (+7.1 ± 1.9 mm Hg); and ICP (+3.6 ± 0.7 mm Hg) compared with baseline values. However, the peak IOP increase was significantly delayed compared with ICP (28 vs. 4 minutes postinjection), resulting in a dramatic translaminar pressure gradient fluctuation.
  
  
  CONCLUSIONS
  Chemical stimulation of DMH/PeF neurons evokes substantial increases in IOP, ICP, and the translaminar pressure gradient in the rat model. Given that the DMH/PeF neurons may be a key effector pathway for circadian regulation of autonomic tone by the suprachiasmatic nucleus, these findings will help elucidate novel mechanisms modulating circadian fluctuations in IOP and the translaminar pressure gradient.
authors.affiliation: Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Samuels
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Hammes
authors.forename: Philip L
authors.initials: PL
authors.lastname: Johnson
authors.forename: Anantha
authors.initials: A
authors.lastname: Shekhar
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: McKinnon
authors.forename: R Rand
authors.initials: RR
authors.lastname: Allingham
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects*; D001640:Bicuculline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D004302:Dorsomedial Hypothalamic Nucleus / Q000187:drug effects* / Q000503:physiopathology; D058787:GABA-A Receptor Antagonists / Q000008:administration & dosage; D005901:Glaucoma / Q000175:diagnosis / Q000503:physiopathology; D007427:Intracranial Pressure / Q000187:drug effects*; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D058787:GABA-A Receptor Antagonists; C017069:bicuculline methiodide; D001640:Bicuculline