Model of infantile spasm syndrome
View Patent ↗Provided are non-human mammals treated with doxorubicin, lipopolysaccharide (LPS), and p-chlorophenylalanine (PCPA), where the mammal exhibits a symptom characteristic of infantile spasms. Also provided are methods of making a non-human mammal exhibit a symptom of infantile spasms. Additionally, methods are provided for screening a compound for the potential to attenuate a symptom of infantile spasms.
1. A rat model of infantile spasms, wherein the rat is administered (i) doxorubicin intracerebrally at day 2, 3 or 4 after birth, (ii) lipopolysaccharide (LPS) intracerebrally at day 2, 3 or 4 after birth, and (iii) p-chlorophenylalanine (PCPA) systemically at day 4, 5 or 6 after birth, wherein the rat exhibits recurrent flexion or extension spasm seizures, and wherein the rat exhibits rapid polyspike activity preceding the seizure on an ictal EEG.
2. The model of claim 1 , wherein the rat is administered (i) doxorubicin intracerebrally at day 3 after birth, (ii) lipopolysaccharide (LPS) intracerebrally at day 3 after birth, and (iii) p-chlorophenylalanine (PCPA) systemically at day 5 after birth.
3. The model of claim 1 , wherein the rat is administered 0.1-5 μg/g doxorubicin, 0.1-5 μg/g, and 30-1000 mg/kg PCPA.
4. The model of claim 1 , wherein the rat is administered 0.5-2 μg/g doxorubicin, 0.5-2 μg/g LPS, and 100-600 mg/kg PCPA.
5. The model of claim 1 , wherein the rat is administered about 1 μg/g doxorubicin, about 1 μg/g LPS, and about 300 mg/kg PCPA.
6. The model of claim 1 , wherein the rat exhibits a recurrent flexion seizure.
7. The model of claim 1 , wherein the rat exhibits an extension spasm seizure.
8. The model of claim 1 , wherein rat further exhibits a deficiency in motor development.
9. The model of claim 8 , wherein the deficiency in motor development is in surface righting, negative geotaxis, cliff aversion, open field activity, rooting, forelimb placing, air righting, eye-opening, horizontal bar, rotarod or a Morris water-maze test.
10. The model of claim 8 , wherein the deficiency in motor development is in surface righting, negative geotaxis or open field activity.
11. A method of making a rat model of infantile spasms, the method comprising administering to the rat (i) doxorubicin intracerebrally at day 2, 3 or 4 after birth, (ii) lipopolysaccharide (LPS) intracerebrally at day 2, 3 or 4 after birth, and (iii) p-chlorophenylalanine (PCPA) systemically at day 4, 5 or 6 after birth, wherein the rat exhibits recurrent flexion or extension spasm seizures, and wherein the rat exhibits rapid polyspike activity preceding the seizure on an ictal EEG.
12. The method of claim 11 , wherein the rat is administered (i) doxorubicin intracerebrally at day 3 after birth, (ii) lipopolysaccharide (LPS) intracerebrally at day 3 after birth, and (iii) p-chlorophenylalanine (PCPA) systemically at day 5 after birth.
13. The method of claim 11 , wherein the rat is administered 0.1-5 μg/g doxorubicin, 0.1-5 μg/g, and 30-1000 mg/kg PCPA.
14. The method of claim 11 , wherein the rat is administered 0.5-2 μg/g doxorubicin, 0.5-2 μg/g LPS, and 100-600 mg/kg PCPA.
15. The method of claim 11 , wherein the rat is administered about 1 μg/g doxorubicin, about 1 μg/g LPS, and about 300 mg/kg PCPA.
16. The method of claim 11 , wherein the rat exhibits a recurrent flexion seizure.
17. The method of claim 11 , wherein the rat exhibits an extension spasm seizure.
18. The method of claim 11 , wherein rat further exhibits a deficiency in motor development.
19. The method of claim 18 , wherein the deficiency in motor development is in surface righting, negative geotaxis, cliff aversion, open field activity, rooting, forelimb placing, air righting, eye-opening, horizontal bar, rotarod or a Morris water-maze test.
20. The method of claim 18 , wherein the deficiency in motor development is in surface righting, negative geotaxis or open field activity.
21. A method of screening a compound for the potential to attenuate a symptom of infantile spasms, the method comprising administering the compound to the rat of claim 1 , and determining whether the compound attenuates a symptom characteristic of infantile spasms in the rat.