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American Heart Association

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Final ID: TP41

Cognitive impairment in the chronic phase of Ischemic Stroke is associated with secondary neurodegeneration in female rats

Abstract Body: Background: Our studies show that intracerebroventricular (ICV) infusion of IGF1 is
neuroprotective in the acute phase of stroke but does not reduce peripheral inflammation or
improve cognitive function in the chronic phase. In contrast, intraperitoneal (IP) injection of
IGF1 did not improve acute phase recovery, but reduced stroke-induced elevation of plasma
inflammatory cytokines, repaired the gut epithelium and attenuated stroke-induced cognitive
impairment. Here we evaluated the extent of chronic neurodegeneration after stroke and the
impact of IP versus ICV treatment with IGF-1.
Method: Middle-aged female rats were subject to MCAo and treated with either ICV-IGF1 or
IP-IGF1 4h after stroke. Animals were tested for cognitive impairment using the Barnes Maze
test 30 days later and terminated thereafter. Brains were collected and processed for block
embedding and sectioning. One set of sections was stained for Weil myelin and imaged using an
Olympus VS120 Slide Scanner. For each section between bregma 2.52 and -5.88, the left and
right hemisphere was manually outlined and measured (QuPath 0.4.3) to obtain hemisphere
volume (μm 3 ). Lateral ventricle in each hemisphere was calculated using slices between bregma
1.56 and -5.88. For callosal thickness, the average dorsal to ventral margin was measured at the
midline in 5 sections of the corpus callosum (0.6 mm apart; bregma 0.3 mm to −0.9 mm).
Results: Histological analysis showed significant reductions in the volume of the ischemic
hemisphere compared to the non-ischemic hemisphere in the ICV-Veh and ICV-IGF1 groups.
Similarly, both groups had enlarged ventricles in the ischemic hemisphere. Sham (no stroke)
animals did not show any left-right differences in hemisphere or ventricular volume. Corpus
callosum width was similar in all groups. In contrast, in the IP-study the volume of the ischemic
hemisphere as compared to the non-ischemic hemisphere were similar in all groups, however,
ventricular enlargement was seen in the ischemic hemisphere of the IP-vehicle group, but not in
the IP-IGF1 or sham groups. Moreover, the midline width of the corpus callosum was
significantly reduced in the IP-Veh group, but not the IP-IGF1 group.
Conclusions: These data suggest that improved cognition in the IP-IGF1 is associated with
preservation of the gray and white matter structures. These data also indicate that targeting
peripheral organs such as the gut presents a fresh approach to enhancing brain health in aging
females.
  • Akbari, Zara  ( Texas A&M , Bryan , Texas , United States )
  • Mani, Kathiresh Kumar  ( Texas A and M University , Bryan , Texas , United States )
  • Pickle, Kaylin  ( Texas A&M University , College Station , Texas , United States )
  • Sohrabji, Farida  ( TEXAS A M HEALTH SCIENCE CENTER , Bryan , Texas , United States )
  • Author Disclosures:
    Zara Akbari: DO NOT have relevant financial relationships | Kathiresh Kumar Mani: DO NOT have relevant financial relationships | Kaylin Pickle: DO NOT have relevant financial relationships | Farida Sohrabji: DO NOT have relevant financial relationships
Meeting Info:
Session Info:

Brain Health Posters II

Thursday, 02/06/2025 , 07:00PM - 07:30PM

Poster Abstract Session

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